---
_id: '14378'
abstract:
- lang: eng
  text: 'Branching morphogenesis is a ubiquitous process that gives rise to high exchange
    surfaces in the vasculature and epithelial organs. Lymphatic capillaries form
    branched networks, which play a key role in the circulation of tissue fluid and
    immune cells. Although mouse models and correlative patient data indicate that
    the lymphatic capillary density directly correlates with functional output, i.e.,
    tissue fluid drainage and trafficking efficiency of dendritic cells, the mechanisms
    ensuring efficient tissue coverage remain poorly understood. Here, we use the
    mouse ear pinna lymphatic vessel network as a model system and combine lineage-tracing,
    genetic perturbations, whole-organ reconstructions and theoretical modeling to
    show that the dermal lymphatic capillaries tile space in an optimal, space-filling
    manner. This coverage is achieved by two complementary mechanisms: initial tissue
    invasion provides a non-optimal global scaffold via self-organized branching morphogenesis,
    while VEGF-C dependent side-branching from existing capillaries rapidly optimizes
    local coverage by directionally targeting low-density regions. With these two
    ingredients, we show that a minimal biophysical model can reproduce quantitatively
    whole-network reconstructions, across development and perturbations. Our results
    show that lymphatic capillary networks can exploit local self-organizing mechanisms
    to achieve tissue-scale optimization.'
acknowledgement: "We thank Dr. Kari Alitalo (University of Helsinki and Wihuri Research
  Institute) for critical reading of the manuscript, providing Vegfc+/− and Clp24ΔEC
  mouse strains and for hosting K.V.’s Academy of Finland postdoctoral researcher
  period (2015–2018). We thank Dr. Sara Wickström (University of Helsinki and Wihuri
  Research Institute) for providing Sox9:Egfp mouse\r\nstrain and the discussions.
  We thank Maija Atuegwu and Tapio Tainola for technical assistance. This work received
  funding from the Academy of Finland (K.V., 315710), Sigrid Juselius Foundation (K.V.),
  University of Helsinki (K.V.), Wihuri Research Institute (K.V.), the ERC under the
  European Union’s Horizon 2020 research and innovation program (grant agreement\r\nNo.
  851288 to E.H.) and under the Marie Skłodowska-Curie grant agreement No. 754411
  (to M.C.U.). Part of the work was carried out with the support of HiLIFE Laboratory
  Animal Centre Core Facility, University of Helsinki, Finland. Imaging was performed
  at the Biomedicum Imaging Unit, Helsinki University, Helsinki, Finland, with the
  support of Biocenter Finland. The AAVpreparations were produced at the Helsinki
  Virus (HelVi) Core."
article_number: '5878'
article_processing_charge: Yes
article_type: original
author:
- first_name: Mehmet C
  full_name: Ucar, Mehmet C
  id: 50B2A802-6007-11E9-A42B-EB23E6697425
  last_name: Ucar
  orcid: 0000-0003-0506-4217
- first_name: Edouard B
  full_name: Hannezo, Edouard B
  id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
  last_name: Hannezo
  orcid: 0000-0001-6005-1561
- first_name: Emmi
  full_name: Tiilikainen, Emmi
  last_name: Tiilikainen
- first_name: Inam
  full_name: Liaqat, Inam
  last_name: Liaqat
- first_name: Emma
  full_name: Jakobsson, Emma
  last_name: Jakobsson
- first_name: Harri
  full_name: Nurmi, Harri
  last_name: Nurmi
- first_name: Kari
  full_name: Vaahtomeri, Kari
  id: 368EE576-F248-11E8-B48F-1D18A9856A87
  last_name: Vaahtomeri
  orcid: 0000-0001-7829-3518
citation:
  ama: Ucar MC, Hannezo EB, Tiilikainen E, et al. Self-organized and directed branching
    results in optimal coverage in developing dermal lymphatic networks. <i>Nature
    Communications</i>. 2023;14. doi:<a href="https://doi.org/10.1038/s41467-023-41456-7">10.1038/s41467-023-41456-7</a>
  apa: Ucar, M. C., Hannezo, E. B., Tiilikainen, E., Liaqat, I., Jakobsson, E., Nurmi,
    H., &#38; Vaahtomeri, K. (2023). Self-organized and directed branching results
    in optimal coverage in developing dermal lymphatic networks. <i>Nature Communications</i>.
    Springer Nature. <a href="https://doi.org/10.1038/s41467-023-41456-7">https://doi.org/10.1038/s41467-023-41456-7</a>
  chicago: Ucar, Mehmet C, Edouard B Hannezo, Emmi Tiilikainen, Inam Liaqat, Emma
    Jakobsson, Harri Nurmi, and Kari Vaahtomeri. “Self-Organized and Directed Branching
    Results in Optimal Coverage in Developing Dermal Lymphatic Networks.” <i>Nature
    Communications</i>. Springer Nature, 2023. <a href="https://doi.org/10.1038/s41467-023-41456-7">https://doi.org/10.1038/s41467-023-41456-7</a>.
  ieee: M. C. Ucar <i>et al.</i>, “Self-organized and directed branching results in
    optimal coverage in developing dermal lymphatic networks,” <i>Nature Communications</i>,
    vol. 14. Springer Nature, 2023.
  ista: Ucar MC, Hannezo EB, Tiilikainen E, Liaqat I, Jakobsson E, Nurmi H, Vaahtomeri
    K. 2023. Self-organized and directed branching results in optimal coverage in
    developing dermal lymphatic networks. Nature Communications. 14, 5878.
  mla: Ucar, Mehmet C., et al. “Self-Organized and Directed Branching Results in Optimal
    Coverage in Developing Dermal Lymphatic Networks.” <i>Nature Communications</i>,
    vol. 14, 5878, Springer Nature, 2023, doi:<a href="https://doi.org/10.1038/s41467-023-41456-7">10.1038/s41467-023-41456-7</a>.
  short: M.C. Ucar, E.B. Hannezo, E. Tiilikainen, I. Liaqat, E. Jakobsson, H. Nurmi,
    K. Vaahtomeri, Nature Communications 14 (2023).
corr_author: '1'
date_created: 2023-10-01T22:01:13Z
date_published: 2023-09-21T00:00:00Z
date_updated: 2025-04-14T07:43:56Z
day: '21'
ddc:
- '570'
department:
- _id: EdHa
doi: 10.1038/s41467-023-41456-7
ec_funded: 1
external_id:
  isi:
  - '001075884500007'
  pmid:
  - '37735168'
file:
- access_level: open_access
  checksum: 4fe5423403f2531753bcd9e0fea48e05
  content_type: application/pdf
  creator: dernst
  date_created: 2023-10-03T07:46:36Z
  date_updated: 2023-10-03T07:46:36Z
  file_id: '14384'
  file_name: 2023_NatureComm_Ucar.pdf
  file_size: 8143264
  relation: main_file
  success: 1
file_date_updated: 2023-10-03T07:46:36Z
fulldoi: https://doi.org/10.1038/s41467-023-41456-7
has_accepted_license: '1'
intvolume: '        14'
isi: 1
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 05943252-7A3F-11EA-A408-12923DDC885E
  call_identifier: H2020
  grant_number: '851288'
  name: Design Principles of Branching Morphogenesis
- _id: 260C2330-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '754411'
  name: ISTplus - Postdoctoral Fellowships
publication: Nature Communications
publication_identifier:
  eissn:
  - 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Self-organized and directed branching results in optimal coverage in developing
  dermal lymphatic networks
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 14
year: '2023'
...
---
_id: '14426'
abstract:
- lang: eng
  text: To meet the physiological demands of the body, organs need to establish a
    functional tissue architecture and adequate size as the embryo develops to adulthood.
    In the liver, uni- and bipotent progenitor differentiation into hepatocytes and
    biliary epithelial cells (BECs), and their relative proportions, comprise the
    functional architecture. Yet, the contribution of individual liver progenitors
    at the organ level to both fates, and their specific proportion, is unresolved.
    Combining mathematical modelling with organ-wide, multispectral FRaeppli-NLS lineage
    tracing in zebrafish, we demonstrate that a precise BEC-to-hepatocyte ratio is
    established (i) fast, (ii) solely by heterogeneous lineage decisions from uni-
    and bipotent progenitors, and (iii) independent of subsequent cell type–specific
    proliferation. Extending lineage tracing to adulthood determined that embryonic
    cells undergo spatially heterogeneous three-dimensional growth associated with
    distinct environments. Strikingly, giant clusters comprising almost half a ventral
    lobe suggest lobe-specific dominant-like growth behaviours. We show substantial
    hepatocyte polyploidy in juveniles representing another hallmark of postembryonic
    liver growth. Our findings uncover heterogeneous progenitor contributions to tissue
    architecture-defining cell type proportions and postembryonic organ growth as
    key mechanisms forming the adult liver.
acknowledgement: "We thank the Ober group for discussion and comments on the manuscript.
  We are grateful to\r\nDr. F. Lemaigre for feedback on the manuscript and Dr. T.
  Piotrowski for invaluable support.\r\nWe thank the department of experimental medicine
  (AEM) in Copenhagen for expert fish\r\ncare. We gratefully acknowledge the DanStem
  Imaging Platform (University of Copenhagen)\r\nfor support and assistance in this
  work.\r\nThis work is supported by Novo Nordisk Foundation grant NNF17CC0027852
  (EAO);\r\nNordisk Foundation grant NNF19OC0058327 (EAO); Novo Nordisk Foundation
  grant\r\nNNF17OC0031204 (PRL); https://novonordiskfonden.dk/en/; Danish National\r\nResearch
  Foundation grant DNRF116 (EAO and AT); https://dg.dk/en/; John and Birthe Meyer\r\nFoundation
  (PRL) and European Research Council (ERC) under the EU Horizon 2020 research and
  Innovation Programme Grant Agreement No. 851288 (EH)."
article_number: e3002315
article_processing_charge: No
article_type: original
author:
- first_name: Iris A.
  full_name: Unterweger, Iris A.
  last_name: Unterweger
- first_name: Julie
  full_name: Klepstad, Julie
  last_name: Klepstad
- first_name: Edouard B
  full_name: Hannezo, Edouard B
  id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
  last_name: Hannezo
  orcid: 0000-0001-6005-1561
- first_name: Pia R.
  full_name: Lundegaard, Pia R.
  last_name: Lundegaard
- first_name: Ala
  full_name: Trusina, Ala
  last_name: Trusina
- first_name: Elke A.
  full_name: Ober, Elke A.
  last_name: Ober
citation:
  ama: Unterweger IA, Klepstad J, Hannezo EB, Lundegaard PR, Trusina A, Ober EA. Lineage
    tracing identifies heterogeneous hepatoblast contribution to cell lineages and
    postembryonic organ growth dynamics. <i>PLoS Biology</i>. 2023;21(10). doi:<a
    href="https://doi.org/10.1371/journal.pbio.3002315">10.1371/journal.pbio.3002315</a>
  apa: Unterweger, I. A., Klepstad, J., Hannezo, E. B., Lundegaard, P. R., Trusina,
    A., &#38; Ober, E. A. (2023). Lineage tracing identifies heterogeneous hepatoblast
    contribution to cell lineages and postembryonic organ growth dynamics. <i>PLoS
    Biology</i>. Public Library of Science. <a href="https://doi.org/10.1371/journal.pbio.3002315">https://doi.org/10.1371/journal.pbio.3002315</a>
  chicago: Unterweger, Iris A., Julie Klepstad, Edouard B Hannezo, Pia R. Lundegaard,
    Ala Trusina, and Elke A. Ober. “Lineage Tracing Identifies Heterogeneous Hepatoblast
    Contribution to Cell Lineages and Postembryonic Organ Growth Dynamics.” <i>PLoS
    Biology</i>. Public Library of Science, 2023. <a href="https://doi.org/10.1371/journal.pbio.3002315">https://doi.org/10.1371/journal.pbio.3002315</a>.
  ieee: I. A. Unterweger, J. Klepstad, E. B. Hannezo, P. R. Lundegaard, A. Trusina,
    and E. A. Ober, “Lineage tracing identifies heterogeneous hepatoblast contribution
    to cell lineages and postembryonic organ growth dynamics,” <i>PLoS Biology</i>,
    vol. 21, no. 10. Public Library of Science, 2023.
  ista: Unterweger IA, Klepstad J, Hannezo EB, Lundegaard PR, Trusina A, Ober EA.
    2023. Lineage tracing identifies heterogeneous hepatoblast contribution to cell
    lineages and postembryonic organ growth dynamics. PLoS Biology. 21(10), e3002315.
  mla: Unterweger, Iris A., et al. “Lineage Tracing Identifies Heterogeneous Hepatoblast
    Contribution to Cell Lineages and Postembryonic Organ Growth Dynamics.” <i>PLoS
    Biology</i>, vol. 21, no. 10, e3002315, Public Library of Science, 2023, doi:<a
    href="https://doi.org/10.1371/journal.pbio.3002315">10.1371/journal.pbio.3002315</a>.
  short: I.A. Unterweger, J. Klepstad, E.B. Hannezo, P.R. Lundegaard, A. Trusina,
    E.A. Ober, PLoS Biology 21 (2023).
date_created: 2023-10-15T22:01:10Z
date_published: 2023-10-04T00:00:00Z
date_updated: 2025-04-14T07:52:27Z
day: '04'
ddc:
- '570'
department:
- _id: EdHa
doi: 10.1371/journal.pbio.3002315
ec_funded: 1
file:
- access_level: open_access
  checksum: 40a2b11b41d70a0e5939f8a52b66e389
  content_type: application/pdf
  creator: dernst
  date_created: 2023-10-16T07:20:49Z
  date_updated: 2023-10-16T07:20:49Z
  file_id: '14431'
  file_name: 2023_PloSBiology_Unterweger.pdf
  file_size: 6193110
  relation: main_file
  success: 1
file_date_updated: 2023-10-16T07:20:49Z
fulldoi: https://doi.org/10.1371/journal.pbio.3002315
has_accepted_license: '1'
intvolume: '        21'
issue: '10'
language:
- iso: eng
month: '10'
oa: 1
oa_version: Published Version
project:
- _id: 05943252-7A3F-11EA-A408-12923DDC885E
  call_identifier: H2020
  grant_number: '851288'
  name: Design Principles of Branching Morphogenesis
publication: PLoS Biology
publication_identifier:
  eissn:
  - 1545-7885
publication_status: published
publisher: Public Library of Science
quality_controlled: '1'
related_material:
  link:
  - relation: software
    url: https://github.com/JulieKlepstad/LiverDevelopment
scopus_import: '1'
status: public
title: Lineage tracing identifies heterogeneous hepatoblast contribution to cell lineages
  and postembryonic organ growth dynamics
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 21
year: '2023'
...
---
_id: '14827'
abstract:
- lang: eng
  text: Understanding complex living systems, which are fundamentally constrained
    by physical phenomena, requires combining experimental data with theoretical physical
    and mathematical models. To develop such models, collaborations between experimental
    cell biologists and theoreticians are increasingly important but these two groups
    often face challenges achieving mutual understanding. To help navigate these challenges,
    this Perspective discusses different modelling approaches, including bottom-up
    hypothesis-driven and top-down data-driven models, and highlights their strengths
    and applications. Using cell mechanics as an example, we explore the integration
    of specific physical models with experimental data from the molecular, cellular
    and tissue level up to multiscale input. We also emphasize the importance of constraining
    model complexity and outline strategies for crosstalk between experimental design
    and model development. Furthermore, we highlight how physical models can provide
    conceptual insights and produce unifying and generalizable frameworks for biological
    phenomena. Overall, this Perspective aims to promote fruitful collaborations that
    advance our understanding of complex biological systems.
acknowledgement: "We thank Prisca Liberali and Edouard Hannezo for many inspiring
  discussions; Mehmet Can Uçar, Nicoletta I Petridou and Qiutan Yang for a critical
  reading of the manuscript, and Claudia Flandoli for the artwork in Figs 2 and 3.
  We would also like to thank The Company of Biologists for the opportunity to attend
  the 2023 workshop on Collective Cell Migration, and all workshop participants for
  discussions.\r\nC.S. was supported by a European Molecular Biology Organization
  (EMBO) Postdoctoral Fellowship (ALTF 660-2020) and Human Frontier Science Program
  (HFSP) Postdoctoral fellowship (LT000746/2021-L). D.B.B. was supported by the NOMIS
  Foundation as a NOMIS Fellow and by an EMBO Postdoctoral Fellowship (ALTF 343-2022)."
article_number: jcs.261515
article_processing_charge: No
article_type: original
author:
- first_name: Cornelia
  full_name: Schwayer, Cornelia
  id: 3436488C-F248-11E8-B48F-1D18A9856A87
  last_name: Schwayer
  orcid: 0000-0001-5130-2226
- first_name: David
  full_name: Brückner, David
  id: e1e86031-6537-11eb-953a-f7ab92be508d
  last_name: Brückner
  orcid: 0000-0001-7205-2975
citation:
  ama: Schwayer C, Brückner D. Connecting theory and experiment in cell and tissue
    mechanics. <i>Journal of Cell Science</i>. 2023;136(24). doi:<a href="https://doi.org/10.1242/jcs.261515">10.1242/jcs.261515</a>
  apa: Schwayer, C., &#38; Brückner, D. (2023). Connecting theory and experiment in
    cell and tissue mechanics. <i>Journal of Cell Science</i>. The Company of Biologists.
    <a href="https://doi.org/10.1242/jcs.261515">https://doi.org/10.1242/jcs.261515</a>
  chicago: Schwayer, Cornelia, and David Brückner. “Connecting Theory and Experiment
    in Cell and Tissue Mechanics.” <i>Journal of Cell Science</i>. The Company of
    Biologists, 2023. <a href="https://doi.org/10.1242/jcs.261515">https://doi.org/10.1242/jcs.261515</a>.
  ieee: C. Schwayer and D. Brückner, “Connecting theory and experiment in cell and
    tissue mechanics,” <i>Journal of Cell Science</i>, vol. 136, no. 24. The Company
    of Biologists, 2023.
  ista: Schwayer C, Brückner D. 2023. Connecting theory and experiment in cell and
    tissue mechanics. Journal of Cell Science. 136(24), jcs. 261515.
  mla: Schwayer, Cornelia, and David Brückner. “Connecting Theory and Experiment in
    Cell and Tissue Mechanics.” <i>Journal of Cell Science</i>, vol. 136, no. 24,
    jcs. 261515, The Company of Biologists, 2023, doi:<a href="https://doi.org/10.1242/jcs.261515">10.1242/jcs.261515</a>.
  short: C. Schwayer, D. Brückner, Journal of Cell Science 136 (2023).
corr_author: '1'
date_created: 2024-01-17T12:46:55Z
date_published: 2023-12-27T00:00:00Z
date_updated: 2025-09-09T14:22:02Z
day: '27'
department:
- _id: EdHa
- _id: CaHe
doi: 10.1242/jcs.261515
external_id:
  isi:
  - '001165394900011'
  pmid:
  - '38149871'
fulldoi: https://doi.org/10.1242/jcs.261515
intvolume: '       136'
isi: 1
issue: '24'
keyword:
- Cell Biology
language:
- iso: eng
month: '12'
oa_version: None
pmid: 1
project:
- _id: 34e2a5b5-11ca-11ed-8bc3-b2265616ef0b
  grant_number: ALTF 343-2022
  name: A mechano-chemical theory for stem cell fate decisions in organoid development
publication: Journal of Cell Science
publication_identifier:
  eissn:
  - 1477-9137
  issn:
  - 0021-9533
publication_status: published
publisher: The Company of Biologists
quality_controlled: '1'
scopus_import: '1'
status: public
title: Connecting theory and experiment in cell and tissue mechanics
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 136
year: '2023'
...
---
OA_place: publisher
_id: '12964'
abstract:
- lang: eng
  text: "Pattern formation is of great importance for its contribution across different
    biological behaviours. During developmental processes for example, patterns of
    chemical gradients are\r\nestablished to determine cell fate and complex tissue
    patterns emerge to define structures such\r\nas limbs and vascular networks. Patterns
    are also seen in collectively migrating groups, for\r\ninstance traveling waves
    of density emerging in moving animal flocks as well as collectively migrating
    cells and tissues. To what extent these biological patterns arise spontaneously
    through\r\nthe local interaction of individual constituents or are dictated by
    higher level instructions is\r\nstill an open question however there is evidence
    for the involvement of both types of process.\r\nWhere patterns arise spontaneously
    there is a long standing interest in how far the interplay\r\nof mechanics, e.g.
    force generation and deformation, and chemistry, e.g. gene regulation\r\nand signaling,
    contributes to the behaviour. This is because many systems are able to both\r\nchemically
    regulate mechanical force production and chemically sense mechanical deformation,\r\nforming
    mechano-chemical feedback loops which can potentially become unstable towards\r\nspatio
    and/or temporal patterning.\r\nWe work with experimental collaborators to investigate
    the possibility that this type of\r\ninteraction drives pattern formation in biological
    systems at different scales. We focus first on\r\ntissue-level ERK-density waves
    observed during the wound healing response across different\r\nsystems where many
    previous studies have proposed that patterns depend on polarized cell\r\nmigration
    and arise from a mechanical flocking-like mechanism. By combining theory with\r\nmechanical
    and optogenetic perturbation experiments on in vitro monolayers we instead find\r\nevidence
    for mechanochemical pattern formation involving only scalar bilateral feedbacks\r\nbetween
    ERK signaling and cell contraction. We perform further modeling and experiment\r\nto
    study how this instability couples with polar cell migration in order to produce
    a robust\r\nand efficient wound healing response. In a following chapter we implement
    ERK-density\r\ncoupling and cell migration in a 2D active vertex model to investigate
    the interaction of\r\nERK-density patterning with different tissue rheologies
    and find that the spatio-temporal\r\ndynamics are able to both locally and globally
    fluidize a tissue across the solid-fluid glass\r\ntransition. In a last chapter
    we move towards lower spatial scales in the context of subcellular\r\npatterning
    of the cell cytoskeleton where we investigate the transition between phases of\r\nspatially
    homogeneous temporal oscillations and chaotic spatio-temporal patterning in the\r\ndynamics
    of myosin and ROCK activities (a motor component of the actomyosin cytoskeleton\r\nand
    its activator). Experimental evidence supports an intrinsic chemical oscillator
    which we\r\nencode in a reaction model and couple to a contractile active gel
    description of the cell cortex.\r\nThe model exhibits phases of chemical oscillations
    and contractile spatial patterning which\r\nreproduce many features of the dynamics
    seen in Drosophila oocyte epithelia in vivo. However,\r\nadditional pharmacological
    perturbations to inhibit myosin contractility leaves the role of\r\ncontractile
    instability unclear. We discuss alternative hypotheses and investigate the possibility\r\nof
    reaction-diffusion instability."
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Daniel R
  full_name: Boocock, Daniel R
  id: 453AF628-F248-11E8-B48F-1D18A9856A87
  last_name: Boocock
  orcid: 0000-0002-1585-2631
citation:
  ama: Boocock DR. Mechanochemical pattern formation across biological scales. 2023.
    doi:<a href="https://doi.org/10.15479/at:ista:12964">10.15479/at:ista:12964</a>
  apa: Boocock, D. R. (2023). <i>Mechanochemical pattern formation across biological
    scales</i>. Institute of Science and Technology Austria. <a href="https://doi.org/10.15479/at:ista:12964">https://doi.org/10.15479/at:ista:12964</a>
  chicago: Boocock, Daniel R. “Mechanochemical Pattern Formation across Biological
    Scales.” Institute of Science and Technology Austria, 2023. <a href="https://doi.org/10.15479/at:ista:12964">https://doi.org/10.15479/at:ista:12964</a>.
  ieee: D. R. Boocock, “Mechanochemical pattern formation across biological scales,”
    Institute of Science and Technology Austria, 2023.
  ista: Boocock DR. 2023. Mechanochemical pattern formation across biological scales.
    Institute of Science and Technology Austria.
  mla: Boocock, Daniel R. <i>Mechanochemical Pattern Formation across Biological Scales</i>.
    Institute of Science and Technology Austria, 2023, doi:<a href="https://doi.org/10.15479/at:ista:12964">10.15479/at:ista:12964</a>.
  short: D.R. Boocock, Mechanochemical Pattern Formation across Biological Scales,
    Institute of Science and Technology Austria, 2023.
corr_author: '1'
date_created: 2023-05-15T14:52:36Z
date_published: 2023-05-17T00:00:00Z
date_updated: 2026-04-07T13:52:57Z
day: '17'
ddc:
- '530'
degree_awarded: PhD
department:
- _id: GradSch
- _id: EdHa
doi: 10.15479/at:ista:12964
ec_funded: 1
file:
- access_level: open_access
  checksum: d51240675fc6dc0e3f5dc0c902695d3a
  content_type: application/pdf
  creator: dboocock
  date_created: 2023-05-17T13:39:54Z
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has_accepted_license: '1'
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc-sa/4.0/
month: '05'
oa: 1
oa_version: Published Version
page: '146'
project:
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '665385'
  name: International IST Doctoral Program
publication_identifier:
  isbn:
  - 978-3-99078-032-9
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
  record:
  - id: '8602'
    relation: part_of_dissertation
    status: public
status: public
supervisor:
- first_name: Edouard B
  full_name: Hannezo, Edouard B
  id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
  last_name: Hannezo
  orcid: 0000-0001-6005-1561
title: Mechanochemical pattern formation across biological scales
tmp:
  image: /images/cc_by_nc_sa.png
  legal_code_url: https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode
  name: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC
    BY-NC-SA 4.0)
  short: CC BY-NC-SA (4.0)
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2023'
...
---
_id: '12837'
abstract:
- lang: eng
  text: As developing tissues grow in size and undergo morphogenetic changes, their
    material properties may be altered. Such changes result from tension dynamics
    at cell contacts or cellular jamming. Yet, in many cases, the cellular mechanisms
    controlling the physical state of growing tissues are unclear. We found that at
    early developmental stages, the epithelium in the developing mouse spinal cord
    maintains both high junctional tension and high fluidity. This is achieved via
    a mechanism in which interkinetic nuclear movements generate cell area dynamics
    that drive extensive cell rearrangements. Over time, the cell proliferation rate
    declines, effectively solidifying the tissue. Thus, unlike well-studied jamming
    transitions, the solidification uncovered here resembles a glass transition that
    depends on the dynamical stresses generated by proliferation and differentiation.
    Our finding that the fluidity of developing epithelia is linked to interkinetic
    nuclear movements and the dynamics of growth is likely to be relevant to multiple
    developing tissues.
acknowledgement: 'We thank S. Hippenmeyer for the reagents and C. P. Heisenberg, J.
  Briscoe and K. Page for comments on the manuscript. This work was supported by IST
  Austria; the European Research Council under Horizon 2020 research and innovation
  programme grant no. 680037 and Horizon Europe grant 101044579 (A.K.); Austrian Science
  Fund (FWF): F78 (Stem Cell Modulation) (A.K.); ISTFELLOW postdoctoral program (A.S.);
  Narodowe Centrum Nauki, Poland SONATA, 2017/26/D/NZ2/00454 (M.Z.); and the Polish
  National Agency for Academic Exchange (M.Z.).'
article_processing_charge: No
article_type: original
author:
- first_name: Laura
  full_name: Bocanegra, Laura
  id: 4896F754-F248-11E8-B48F-1D18A9856A87
  last_name: Bocanegra
- first_name: Amrita
  full_name: Singh, Amrita
  id: 76250f9f-3a21-11eb-9a80-a6180a0d7958
  last_name: Singh
- first_name: Edouard B
  full_name: Hannezo, Edouard B
  id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
  last_name: Hannezo
  orcid: 0000-0001-6005-1561
- first_name: Marcin P
  full_name: Zagórski, Marcin P
  id: 343DA0DC-F248-11E8-B48F-1D18A9856A87
  last_name: Zagórski
  orcid: 0000-0001-7896-7762
- first_name: Anna
  full_name: Kicheva, Anna
  id: 3959A2A0-F248-11E8-B48F-1D18A9856A87
  last_name: Kicheva
  orcid: 0000-0003-4509-4998
citation:
  ama: Bocanegra L, Singh A, Hannezo EB, Zagórski MP, Kicheva A. Cell cycle dynamics
    control fluidity of the developing mouse neuroepithelium. <i>Nature Physics</i>.
    2023;19:1050-1058. doi:<a href="https://doi.org/10.1038/s41567-023-01977-w">10.1038/s41567-023-01977-w</a>
  apa: Bocanegra, L., Singh, A., Hannezo, E. B., Zagórski, M. P., &#38; Kicheva, A.
    (2023). Cell cycle dynamics control fluidity of the developing mouse neuroepithelium.
    <i>Nature Physics</i>. Springer Nature. <a href="https://doi.org/10.1038/s41567-023-01977-w">https://doi.org/10.1038/s41567-023-01977-w</a>
  chicago: Bocanegra, Laura, Amrita Singh, Edouard B Hannezo, Marcin P Zagórski, and
    Anna Kicheva. “Cell Cycle Dynamics Control Fluidity of the Developing Mouse Neuroepithelium.”
    <i>Nature Physics</i>. Springer Nature, 2023. <a href="https://doi.org/10.1038/s41567-023-01977-w">https://doi.org/10.1038/s41567-023-01977-w</a>.
  ieee: L. Bocanegra, A. Singh, E. B. Hannezo, M. P. Zagórski, and A. Kicheva, “Cell
    cycle dynamics control fluidity of the developing mouse neuroepithelium,” <i>Nature
    Physics</i>, vol. 19. Springer Nature, pp. 1050–1058, 2023.
  ista: Bocanegra L, Singh A, Hannezo EB, Zagórski MP, Kicheva A. 2023. Cell cycle
    dynamics control fluidity of the developing mouse neuroepithelium. Nature Physics.
    19, 1050–1058.
  mla: Bocanegra, Laura, et al. “Cell Cycle Dynamics Control Fluidity of the Developing
    Mouse Neuroepithelium.” <i>Nature Physics</i>, vol. 19, Springer Nature, 2023,
    pp. 1050–58, doi:<a href="https://doi.org/10.1038/s41567-023-01977-w">10.1038/s41567-023-01977-w</a>.
  short: L. Bocanegra, A. Singh, E.B. Hannezo, M.P. Zagórski, A. Kicheva, Nature Physics
    19 (2023) 1050–1058.
corr_author: '1'
date_created: 2023-04-16T22:01:09Z
date_published: 2023-07-01T00:00:00Z
date_updated: 2026-10-20T22:30:20Z
day: '01'
ddc:
- '570'
department:
- _id: EdHa
- _id: AnKi
doi: 10.1038/s41567-023-01977-w
ec_funded: 1
external_id:
  isi:
  - '000964029300003'
  pmid:
  - '37456593'
file:
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file_date_updated: 2023-10-04T11:13:28Z
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intvolume: '        19'
isi: 1
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
page: 1050-1058
pmid: 1
project:
- _id: B6FC0238-B512-11E9-945C-1524E6697425
  call_identifier: H2020
  grant_number: '680037'
  name: Coordination of Patterning And Growth In the Spinal Cord
- _id: bd7e737f-d553-11ed-ba76-d69ffb5ee3aa
  grant_number: '101044579'
  name: Mechanisms of tissue size regulation in spinal cord development
- _id: 059DF620-7A3F-11EA-A408-12923DDC885E
  grant_number: F7802
  name: Stem Cell Modulation in Neural Development and Regeneration/ P02-Morphogen
    control of growth and pattern in the spinal cord
- _id: 25681D80-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '291734'
  name: International IST Postdoc Fellowship Programme
publication: Nature Physics
publication_identifier:
  eissn:
  - 1745-2481
  issn:
  - 1745-2473
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
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  - id: '13081'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: Cell cycle dynamics control fluidity of the developing mouse neuroepithelium
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 19
year: '2023'
...
---
_id: '14274'
abstract:
- lang: eng
  text: Immune responses rely on the rapid and coordinated migration of leukocytes.
    Whereas it is well established that single-cell migration is often guided by gradients
    of chemokines and other chemoattractants, it remains poorly understood how these
    gradients are generated, maintained, and modulated. By combining experimental
    data with theory on leukocyte chemotaxis guided by the G protein–coupled receptor
    (GPCR) CCR7, we demonstrate that in addition to its role as the sensory receptor
    that steers migration, CCR7 also acts as a generator and a modulator of chemotactic
    gradients. Upon exposure to the CCR7 ligand CCL19, dendritic cells (DCs) effectively
    internalize the receptor and ligand as part of the canonical GPCR desensitization
    response. We show that CCR7 internalization also acts as an effective sink for
    the chemoattractant, dynamically shaping the spatiotemporal distribution of the
    chemokine. This mechanism drives complex collective migration patterns, enabling
    DCs to create or sharpen chemotactic gradients. We further show that these self-generated
    gradients can sustain the long-range guidance of DCs, adapt collective migration
    patterns to the size and geometry of the environment, and provide a guidance cue
    for other comigrating cells. Such a dual role of CCR7 as a GPCR that both senses
    and consumes its ligand can thus provide a novel mode of cellular self-organization.
acknowledgement: "We thank I. de Vries and the Scientific Service Units (Life Sciences,
  Bioimaging, Nanofabrication, Preclinical and Miba Machine Shop) of the Institute
  of Science and Technology Austria for excellent support, as well as all the rotation
  students assisting in the laboratory work (B. Zens, H. Schön, and D. Babic).\r\nThis
  work was supported by grants from the European Research Council under the European
  Union’s Horizon 2020 research to M.S. (grant agreement no. 724373) and to E.H. (grant
  agreement no. 851288), and a grant by the Austrian Science Fund (DK Nanocell W1250-B20)
  to M.S. J.A. was supported by the Jenny and Antti Wihuri Foundation and Research
  Council of Finland's Flagship Programme InFLAMES (decision number: 357910). M.C.U.
  was supported by the European Union’s Horizon 2020 research and innovation programme
  under the Marie Skłodowska-Curie grant agreement no. 754411."
article_number: adc9584
article_processing_charge: No
article_type: original
author:
- first_name: Jonna H
  full_name: Alanko, Jonna H
  id: 2CC12E8C-F248-11E8-B48F-1D18A9856A87
  last_name: Alanko
  orcid: 0000-0002-7698-3061
- first_name: Mehmet C
  full_name: Ucar, Mehmet C
  id: 50B2A802-6007-11E9-A42B-EB23E6697425
  last_name: Ucar
  orcid: 0000-0003-0506-4217
- first_name: Nikola
  full_name: Canigova, Nikola
  id: 3795523E-F248-11E8-B48F-1D18A9856A87
  last_name: Canigova
  orcid: 0000-0002-8518-5926
- first_name: Julian A
  full_name: Stopp, Julian A
  id: 489E3F00-F248-11E8-B48F-1D18A9856A87
  last_name: Stopp
- first_name: Jan
  full_name: Schwarz, Jan
  id: 346C1EC6-F248-11E8-B48F-1D18A9856A87
  last_name: Schwarz
- first_name: Jack
  full_name: Merrin, Jack
  id: 4515C308-F248-11E8-B48F-1D18A9856A87
  last_name: Merrin
  orcid: 0000-0001-5145-4609
- first_name: Edouard B
  full_name: Hannezo, Edouard B
  id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
  last_name: Hannezo
  orcid: 0000-0001-6005-1561
- first_name: Michael K
  full_name: Sixt, Michael K
  id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
  last_name: Sixt
  orcid: 0000-0002-6620-9179
citation:
  ama: Alanko JH, Ucar MC, Canigova N, et al. CCR7 acts as both a sensor and a sink
    for CCL19 to coordinate collective leukocyte migration. <i>Science Immunology</i>.
    2023;8(87). doi:<a href="https://doi.org/10.1126/sciimmunol.adc9584">10.1126/sciimmunol.adc9584</a>
  apa: Alanko, J. H., Ucar, M. C., Canigova, N., Stopp, J. A., Schwarz, J., Merrin,
    J., … Sixt, M. K. (2023). CCR7 acts as both a sensor and a sink for CCL19 to coordinate
    collective leukocyte migration. <i>Science Immunology</i>. American Association
    for the Advancement of Science. <a href="https://doi.org/10.1126/sciimmunol.adc9584">https://doi.org/10.1126/sciimmunol.adc9584</a>
  chicago: Alanko, Jonna H, Mehmet C Ucar, Nikola Canigova, Julian A Stopp, Jan Schwarz,
    Jack Merrin, Edouard B Hannezo, and Michael K Sixt. “CCR7 Acts as Both a Sensor
    and a Sink for CCL19 to Coordinate Collective Leukocyte Migration.” <i>Science
    Immunology</i>. American Association for the Advancement of Science, 2023. <a
    href="https://doi.org/10.1126/sciimmunol.adc9584">https://doi.org/10.1126/sciimmunol.adc9584</a>.
  ieee: J. H. Alanko <i>et al.</i>, “CCR7 acts as both a sensor and a sink for CCL19
    to coordinate collective leukocyte migration,” <i>Science Immunology</i>, vol.
    8, no. 87. American Association for the Advancement of Science, 2023.
  ista: Alanko JH, Ucar MC, Canigova N, Stopp JA, Schwarz J, Merrin J, Hannezo EB,
    Sixt MK. 2023. CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective
    leukocyte migration. Science Immunology. 8(87), adc9584.
  mla: Alanko, Jonna H., et al. “CCR7 Acts as Both a Sensor and a Sink for CCL19 to
    Coordinate Collective Leukocyte Migration.” <i>Science Immunology</i>, vol. 8,
    no. 87, adc9584, American Association for the Advancement of Science, 2023, doi:<a
    href="https://doi.org/10.1126/sciimmunol.adc9584">10.1126/sciimmunol.adc9584</a>.
  short: J.H. Alanko, M.C. Ucar, N. Canigova, J.A. Stopp, J. Schwarz, J. Merrin, E.B.
    Hannezo, M.K. Sixt, Science Immunology 8 (2023).
corr_author: '1'
date_created: 2023-09-06T08:07:51Z
date_published: 2023-09-01T00:00:00Z
date_updated: 2026-10-20T22:30:35Z
day: '01'
ddc:
- '570'
department:
- _id: MiSi
- _id: EdHa
- _id: NanoFab
doi: 10.1126/sciimmunol.adc9584
ec_funded: 1
external_id:
  isi:
  - '001062110600003'
  pmid:
  - '37656776'
fulldoi: https://doi.org/10.1126/sciimmunol.adc9584
intvolume: '         8'
isi: 1
issue: '87'
keyword:
- General Medicine
- Immunology
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1126/sciimmunol.adc9584
month: '09'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 25FE9508-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '724373'
  name: Cellular Navigation Along Spatial Gradients
- _id: 05943252-7A3F-11EA-A408-12923DDC885E
  call_identifier: H2020
  grant_number: '851288'
  name: Design Principles of Branching Morphogenesis
- _id: 265E2996-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: W01250-B20
  name: Nano-Analytics of Cellular Systems
- _id: 260C2330-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '754411'
  name: ISTplus - Postdoctoral Fellowships
publication: Science Immunology
publication_identifier:
  issn:
  - 2470-9468
publication_status: published
publisher: American Association for the Advancement of Science
quality_controlled: '1'
related_material:
  record:
  - id: '14279'
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    status: public
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    status: public
  - id: '19745'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte
  migration
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 8
year: '2023'
...
---
_id: '13116'
abstract:
- lang: eng
  text: 'The emergence of large-scale order in self-organized systems relies on local
    interactions between individual components. During bacterial cell division, FtsZ
    -- a prokaryotic homologue of the eukaryotic protein tubulin -- polymerizes into
    treadmilling filaments that further organize into a cytoskeletal ring. In vitro,
    FtsZ filaments can form dynamic chiral assemblies. However, how the active and
    passive properties of individual filaments relate to these large-scale self-organized
    structures remains poorly understood. Here, we connect single filament properties
    with the mesoscopic scale by combining minimal active matter simulations and biochemical
    reconstitution experiments. We show that density and flexibility of active chiral
    filaments define their global order. At intermediate densities, curved, flexible
    filaments organize into chiral rings and polar bands. An effectively nematic organization
    dominates for high densities and for straight, mutant filaments with increased
    rigidity. Our predicted phase diagram captures these features quantitatively,
    demonstrating how the flexibility, density and chirality of active filaments affect
    their collective behaviour. Our findings shed light on the fundamental properties
    of active chiral matter and explain how treadmilling FtsZ filaments organize during
    bacterial cell division. '
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
acknowledgement: 'This work was supported by the European Research Council through
  grant ERC 2015-StG-679239 and by the Austrian Science Fund (FWF) StandAlone P34607
  to M.L., B. P.M.  was also supported by the Kanazawa University WPI- NanoLSI Bio-SPM
  collaborative research program. Z.D. has received funding from Doctoral Programme
  of the Austrian Academy of Sciences (OeAW): Grant agreement 26360. We thank Jan
  Brugues (MPI CBG, Dresden, Germany), Andela Saric (ISTA, Klosterneuburg, Austria),
  Daniel Pearce (Uni Geneva, Switzerland) for valuable scientific input and comments
  on the manuscript. We are also thankful for the support by the Scientific Service
  Units (SSU) of IST Austria through resources provided by the Imaging and Optics
  Facility (IOF) and the Lab Support Facility (LSF). '
article_processing_charge: No
author:
- first_name: Zuzana
  full_name: Dunajova, Zuzana
  id: 4B39F286-F248-11E8-B48F-1D18A9856A87
  last_name: Dunajova
- first_name: Batirtze
  full_name: Prats Mateu, Batirtze
  id: 299FE892-F248-11E8-B48F-1D18A9856A87
  last_name: Prats Mateu
- first_name: Philipp
  full_name: Radler, Philipp
  id: 40136C2A-F248-11E8-B48F-1D18A9856A87
  last_name: Radler
  orcid: '0000-0001-9198-2182 '
- first_name: Keesiang
  full_name: Lim, Keesiang
  last_name: Lim
- first_name: Dörte
  full_name: Brandis, Dörte
  last_name: Brandis
- first_name: Philipp
  full_name: Velicky, Philipp
  id: 39BDC62C-F248-11E8-B48F-1D18A9856A87
  last_name: Velicky
  orcid: 0000-0002-2340-7431
- first_name: Johann G
  full_name: Danzl, Johann G
  id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
  last_name: Danzl
  orcid: 0000-0001-8559-3973
- first_name: Richard W.
  full_name: Wong, Richard W.
  last_name: Wong
- first_name: Jens
  full_name: Elgeti, Jens
  last_name: Elgeti
- first_name: Edouard B
  full_name: Hannezo, Edouard B
  id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
  last_name: Hannezo
  orcid: 0000-0001-6005-1561
- first_name: Martin
  full_name: Loose, Martin
  id: 462D4284-F248-11E8-B48F-1D18A9856A87
  last_name: Loose
  orcid: 0000-0001-7309-9724
citation:
  ama: Dunajova Z, Prats Mateu B, Radler P, et al. Chiral and nematic phases of flexible
    active filaments. 2023. doi:<a href="https://doi.org/10.15479/AT:ISTA:13116">10.15479/AT:ISTA:13116</a>
  apa: Dunajova, Z., Prats Mateu, B., Radler, P., Lim, K., Brandis, D., Velicky, P.,
    … Loose, M. (2023). Chiral and nematic phases of flexible active filaments. Institute
    of Science and Technology Austria. <a href="https://doi.org/10.15479/AT:ISTA:13116">https://doi.org/10.15479/AT:ISTA:13116</a>
  chicago: Dunajova, Zuzana, Batirtze Prats Mateu, Philipp Radler, Keesiang Lim, Dörte
    Brandis, Philipp Velicky, Johann G Danzl, et al. “Chiral and Nematic Phases of
    Flexible Active Filaments.” Institute of Science and Technology Austria, 2023.
    <a href="https://doi.org/10.15479/AT:ISTA:13116">https://doi.org/10.15479/AT:ISTA:13116</a>.
  ieee: Z. Dunajova <i>et al.</i>, “Chiral and nematic phases of flexible active filaments.”
    Institute of Science and Technology Austria, 2023.
  ista: Dunajova Z, Prats Mateu B, Radler P, Lim K, Brandis D, Velicky P, Danzl JG,
    Wong RW, Elgeti J, Hannezo EB, Loose M. 2023. Chiral and nematic phases of flexible
    active filaments, Institute of Science and Technology Austria, <a href="https://doi.org/10.15479/AT:ISTA:13116">10.15479/AT:ISTA:13116</a>.
  mla: Dunajova, Zuzana, et al. <i>Chiral and Nematic Phases of Flexible Active Filaments</i>.
    Institute of Science and Technology Austria, 2023, doi:<a href="https://doi.org/10.15479/AT:ISTA:13116">10.15479/AT:ISTA:13116</a>.
  short: Z. Dunajova, B. Prats Mateu, P. Radler, K. Lim, D. Brandis, P. Velicky, J.G.
    Danzl, R.W. Wong, J. Elgeti, E.B. Hannezo, M. Loose, (2023).
corr_author: '1'
date_created: 2023-06-02T12:30:40Z
date_published: 2023-07-26T00:00:00Z
date_updated: 2026-10-20T22:31:29Z
day: '26'
ddc:
- '539'
department:
- _id: MaLo
- _id: EdHa
- _id: JoDa
doi: 10.15479/AT:ISTA:13116
ec_funded: 1
file:
- access_level: open_access
  checksum: 4b4ec5d4df7672b3af5ba23b126b171b
  content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
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fulldoi: https://doi.org/10.15479/AT:ISTA:13116
has_accepted_license: '1'
month: '07'
oa: 1
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project:
- _id: 2595697A-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
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  name: Self-Organization of the Bacterial Cell
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  grant_number: P34607
  name: In vitro reconstitution of bacterial cell division
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  grant_number: '26360'
  name: Motile active matter models of migrating cells and chiral filaments
publisher: Institute of Science and Technology Austria
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title: Chiral and nematic phases of flexible active filaments
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: research_data
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2023'
...
---
_id: '13314'
abstract:
- lang: eng
  text: The emergence of large-scale order in self-organized systems relies on local
    interactions between individual components. During bacterial cell division, FtsZ—a
    prokaryotic homologue of the eukaryotic protein tubulin—polymerizes into treadmilling
    filaments that further organize into a cytoskeletal ring. In vitro, FtsZ filaments
    can form dynamic chiral assemblies. However, how the active and passive properties
    of individual filaments relate to these large-scale self-organized structures
    remains poorly understood. Here we connect single-filament properties with the
    mesoscopic scale by combining minimal active matter simulations and biochemical
    reconstitution experiments. We show that the density and flexibility of active
    chiral filaments define their global order. At intermediate densities, curved,
    flexible filaments organize into chiral rings and polar bands. An effectively
    nematic organization dominates for high densities and for straight, mutant filaments
    with increased rigidity. Our predicted phase diagram quantitatively captures these
    features, demonstrating how the flexibility, density and chirality of the active
    filaments affect their collective behaviour. Our findings shed light on the fundamental
    properties of active chiral matter and explain how treadmilling FtsZ filaments
    organize during bacterial cell division.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
acknowledgement: 'This work was supported by the European Research Council through
  grant ERC 2015-StG-679239 and by the Austrian Science Fund (FWF) StandAlone P34607
  to M.L., B. P.M. was also supported by the Kanazawa University WPI- NanoLSI Bio-SPM
  collaborative research program. Z.D. has received funding from Doctoral Programme
  of the Austrian Academy of Sciences (OeAW): Grant agreement 26360. We thank Jan
  Brugues (MPI CBG, Dresden, Germany), Andela Saric (ISTA, Klosterneuburg, Austria),
  Daniel Pearce (Uni Geneva, Switzerland) for valuable scientific input and comments
  on the manuscript. We are also thankful for the support by the Scientific Service
  Units (SSU) of IST Austria through resources provided by the Imaging and Optics
  Facility (IOF) and the Lab Support Facility (LSF).'
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Zuzana
  full_name: Dunajova, Zuzana
  id: 4B39F286-F248-11E8-B48F-1D18A9856A87
  last_name: Dunajova
- first_name: Batirtze
  full_name: Prats Mateu, Batirtze
  id: 299FE892-F248-11E8-B48F-1D18A9856A87
  last_name: Prats Mateu
- first_name: Philipp
  full_name: Radler, Philipp
  id: 40136C2A-F248-11E8-B48F-1D18A9856A87
  last_name: Radler
  orcid: '0000-0001-9198-2182 '
- first_name: Keesiang
  full_name: Lim, Keesiang
  last_name: Lim
- first_name: Dörte
  full_name: Brandis, Dörte
  id: 21d64d35-f128-11eb-9611-b8bcca7a12fd
  last_name: Brandis
- first_name: Philipp
  full_name: Velicky, Philipp
  id: 39BDC62C-F248-11E8-B48F-1D18A9856A87
  last_name: Velicky
  orcid: 0000-0002-2340-7431
- first_name: Johann G
  full_name: Danzl, Johann G
  id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
  last_name: Danzl
  orcid: 0000-0001-8559-3973
- first_name: Richard W.
  full_name: Wong, Richard W.
  last_name: Wong
- first_name: Jens
  full_name: Elgeti, Jens
  last_name: Elgeti
- first_name: Edouard B
  full_name: Hannezo, Edouard B
  id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
  last_name: Hannezo
  orcid: 0000-0001-6005-1561
- first_name: Martin
  full_name: Loose, Martin
  id: 462D4284-F248-11E8-B48F-1D18A9856A87
  last_name: Loose
  orcid: 0000-0001-7309-9724
citation:
  ama: Dunajova Z, Prats Mateu B, Radler P, et al. Chiral and nematic phases of flexible
    active filaments. <i>Nature Physics</i>. 2023;19:1916-1926. doi:<a href="https://doi.org/10.1038/s41567-023-02218-w">10.1038/s41567-023-02218-w</a>
  apa: Dunajova, Z., Prats Mateu, B., Radler, P., Lim, K., Brandis, D., Velicky, P.,
    … Loose, M. (2023). Chiral and nematic phases of flexible active filaments. <i>Nature
    Physics</i>. Springer Nature. <a href="https://doi.org/10.1038/s41567-023-02218-w">https://doi.org/10.1038/s41567-023-02218-w</a>
  chicago: Dunajova, Zuzana, Batirtze Prats Mateu, Philipp Radler, Keesiang Lim, Dörte
    Brandis, Philipp Velicky, Johann G Danzl, et al. “Chiral and Nematic Phases of
    Flexible Active Filaments.” <i>Nature Physics</i>. Springer Nature, 2023. <a href="https://doi.org/10.1038/s41567-023-02218-w">https://doi.org/10.1038/s41567-023-02218-w</a>.
  ieee: Z. Dunajova <i>et al.</i>, “Chiral and nematic phases of flexible active filaments,”
    <i>Nature Physics</i>, vol. 19. Springer Nature, pp. 1916–1926, 2023.
  ista: Dunajova Z, Prats Mateu B, Radler P, Lim K, Brandis D, Velicky P, Danzl JG,
    Wong RW, Elgeti J, Hannezo EB, Loose M. 2023. Chiral and nematic phases of flexible
    active filaments. Nature Physics. 19, 1916–1926.
  mla: Dunajova, Zuzana, et al. “Chiral and Nematic Phases of Flexible Active Filaments.”
    <i>Nature Physics</i>, vol. 19, Springer Nature, 2023, pp. 1916–26, doi:<a href="https://doi.org/10.1038/s41567-023-02218-w">10.1038/s41567-023-02218-w</a>.
  short: Z. Dunajova, B. Prats Mateu, P. Radler, K. Lim, D. Brandis, P. Velicky, J.G.
    Danzl, R.W. Wong, J. Elgeti, E.B. Hannezo, M. Loose, Nature Physics 19 (2023)
    1916–1926.
corr_author: '1'
date_created: 2023-07-27T14:44:45Z
date_published: 2023-12-01T00:00:00Z
date_updated: 2026-10-20T22:31:29Z
day: '01'
ddc:
- '530'
department:
- _id: JoDa
- _id: EdHa
- _id: MaLo
- _id: GradSch
doi: 10.1038/s41567-023-02218-w
ec_funded: 1
external_id:
  isi:
  - '001178645300041'
  pmid:
  - '38075437'
file:
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  checksum: bc7673ca07d37309013a86166577b2f7
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fulldoi: https://doi.org/10.1038/s41567-023-02218-w
has_accepted_license: '1'
intvolume: '        19'
isi: 1
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
page: 1916-1926
pmid: 1
project:
- _id: 2595697A-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '679239'
  name: Self-Organization of the Bacterial Cell
- _id: fc38323b-9c52-11eb-aca3-ff8afb4a011d
  grant_number: P34607
  name: In vitro reconstitution of bacterial cell division
- _id: 34d75525-11ca-11ed-8bc3-89b6307fee9d
  grant_number: '26360'
  name: Motile active matter models of migrating cells and chiral filaments
publication: Nature Physics
publication_identifier:
  eissn:
  - 1745-2481
  issn:
  - 1745-2473
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
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    status: public
scopus_import: '1'
status: public
title: Chiral and nematic phases of flexible active filaments
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 19
year: '2023'
...
---
_id: '10825'
abstract:
- lang: eng
  text: In development, lineage segregation is coordinated in time and space. An important
    example is the mammalian inner cell mass, in which the primitive endoderm (PrE,
    founder of the yolk sac) physically segregates from the epiblast (EPI, founder
    of the fetus). While the molecular requirements have been well studied, the physical
    mechanisms determining spatial segregation between EPI and PrE remain elusive.
    Here, we investigate the mechanical basis of EPI and PrE sorting. We find that
    rather than the differences in static cell surface mechanical parameters as in
    classical sorting models, it is the differences in surface fluctuations that robustly
    ensure physical lineage sorting. These differential surface fluctuations systematically
    correlate with differential cellular fluidity, which we propose together constitute
    a non-equilibrium sorting mechanism for EPI and PrE lineages. By combining experiments
    and modeling, we identify cell surface dynamics as a key factor orchestrating
    the correct spatial segregation of the founder embryonic lineages.
acknowledgement: We are grateful to H. Niwa for Dox regulatable PB vector; G. Charras
  for EzrinT567D cDNA; K. Jones for tdTomato ESCs, R26-Confetti ESCs, and laboratory
  assistance; M. Kinoshita for pPB-CAG-H2B-BFP plasmid; P. Humphreys and D. Clements
  for imaging support; G. Chu, P. Attlesey, and staff for animal husbandry; S. Pallett
  for laboratory assistance; C. Mulas for critical feedback on the project; T. Boroviak
  for single-cell RNA-seq; the EMBL Genomics Core Facility for sequencing; and M.
  Merkel for developing and sharing the original version of the 3D Voronoi code. This
  work was financially supported by BBSRC ( BB/Moo4023/1 and BB/T007044/1 to K.J.C.
  and J.N., Alert16 grant BB/R000042 to E.K.P.), Leverhulme Trust ( RPG-2014-080 to
  K.J.C. and J.N.), European Research Council ( 772798 -CellFateTech to K.J.C., 311637
  -MorphoCorDiv and 820188 -NanoMechShape to E.K.P., Starting Grant 851288 to E.H.,
  and 772426 -MeChemGui to K.F.), the Isaac Newton Trust (to E.K.P.), Medical Research
  Council UK (MRC program award MC_UU_00012/5 to E.K.P.), the European Union’s Horizon
  2020 research and innovation program under the Marie Sklodowska-Curie grant agreement
  no. 641639 ( ITN Biopol , H.D.B. and E.K.P.), the Alexander von Humboldt Foundation
  (Alexander von Humboldt Professorship to K.F.), EMBO ALTF 522-2021 (to P.S.), Centre
  for Trophoblast Research (Next Generation fellowship to S.A.), and JSPS Overseas
  Research Fellowships (to A.Y.). The Wellcome-MRC Cambridge Stem Cell Institute receives
  core funding from Wellcome Trust ( 203151/Z/16/Z ) and MRC ( MC_PC_17230 ). For
  the purpose of open access, the author has applied a CC BY public copyright licence
  to any Author Accepted Manuscript version arising from this submission.
article_processing_charge: No
article_type: original
author:
- first_name: Ayaka
  full_name: Yanagida, Ayaka
  last_name: Yanagida
- first_name: Elena
  full_name: Corujo-Simon, Elena
  last_name: Corujo-Simon
- first_name: Christopher K.
  full_name: Revell, Christopher K.
  last_name: Revell
- first_name: Preeti
  full_name: Sahu, Preeti
  id: 55BA52EE-A185-11EA-88FD-18AD3DDC885E
  last_name: Sahu
- first_name: Giuliano G.
  full_name: Stirparo, Giuliano G.
  last_name: Stirparo
- first_name: Irene M.
  full_name: Aspalter, Irene M.
  last_name: Aspalter
- first_name: Alex K.
  full_name: Winkel, Alex K.
  last_name: Winkel
- first_name: Ruby
  full_name: Peters, Ruby
  last_name: Peters
- first_name: Henry
  full_name: De Belly, Henry
  last_name: De Belly
- first_name: Davide A.D.
  full_name: Cassani, Davide A.D.
  last_name: Cassani
- first_name: Sarra
  full_name: Achouri, Sarra
  last_name: Achouri
- first_name: Raphael
  full_name: Blumenfeld, Raphael
  last_name: Blumenfeld
- first_name: Kristian
  full_name: Franze, Kristian
  last_name: Franze
- first_name: Edouard B
  full_name: Hannezo, Edouard B
  id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
  last_name: Hannezo
  orcid: 0000-0001-6005-1561
- first_name: Ewa K.
  full_name: Paluch, Ewa K.
  last_name: Paluch
- first_name: Jennifer
  full_name: Nichols, Jennifer
  last_name: Nichols
- first_name: Kevin J.
  full_name: Chalut, Kevin J.
  last_name: Chalut
citation:
  ama: Yanagida A, Corujo-Simon E, Revell CK, et al. Cell surface fluctuations regulate
    early embryonic lineage sorting. <i>Cell</i>. 2022;185(5):777-793.e20. doi:<a
    href="https://doi.org/10.1016/j.cell.2022.01.022">10.1016/j.cell.2022.01.022</a>
  apa: Yanagida, A., Corujo-Simon, E., Revell, C. K., Sahu, P., Stirparo, G. G., Aspalter,
    I. M., … Chalut, K. J. (2022). Cell surface fluctuations regulate early embryonic
    lineage sorting. <i>Cell</i>. Cell Press. <a href="https://doi.org/10.1016/j.cell.2022.01.022">https://doi.org/10.1016/j.cell.2022.01.022</a>
  chicago: Yanagida, Ayaka, Elena Corujo-Simon, Christopher K. Revell, Preeti Sahu,
    Giuliano G. Stirparo, Irene M. Aspalter, Alex K. Winkel, et al. “Cell Surface
    Fluctuations Regulate Early Embryonic Lineage Sorting.” <i>Cell</i>. Cell Press,
    2022. <a href="https://doi.org/10.1016/j.cell.2022.01.022">https://doi.org/10.1016/j.cell.2022.01.022</a>.
  ieee: A. Yanagida <i>et al.</i>, “Cell surface fluctuations regulate early embryonic
    lineage sorting,” <i>Cell</i>, vol. 185, no. 5. Cell Press, p. 777–793.e20, 2022.
  ista: Yanagida A, Corujo-Simon E, Revell CK, Sahu P, Stirparo GG, Aspalter IM, Winkel
    AK, Peters R, De Belly H, Cassani DAD, Achouri S, Blumenfeld R, Franze K, Hannezo
    EB, Paluch EK, Nichols J, Chalut KJ. 2022. Cell surface fluctuations regulate
    early embryonic lineage sorting. Cell. 185(5), 777–793.e20.
  mla: Yanagida, Ayaka, et al. “Cell Surface Fluctuations Regulate Early Embryonic
    Lineage Sorting.” <i>Cell</i>, vol. 185, no. 5, Cell Press, 2022, p. 777–793.e20,
    doi:<a href="https://doi.org/10.1016/j.cell.2022.01.022">10.1016/j.cell.2022.01.022</a>.
  short: A. Yanagida, E. Corujo-Simon, C.K. Revell, P. Sahu, G.G. Stirparo, I.M. Aspalter,
    A.K. Winkel, R. Peters, H. De Belly, D.A.D. Cassani, S. Achouri, R. Blumenfeld,
    K. Franze, E.B. Hannezo, E.K. Paluch, J. Nichols, K.J. Chalut, Cell 185 (2022)
    777–793.e20.
date_created: 2022-03-06T23:01:52Z
date_published: 2022-02-22T00:00:00Z
date_updated: 2025-07-10T11:50:00Z
day: '22'
ddc:
- '570'
department:
- _id: EdHa
doi: 10.1016/j.cell.2022.01.022
ec_funded: 1
external_id:
  isi:
  - '000796293700007'
  pmid:
  - '35196500'
file:
- access_level: open_access
  checksum: ae305060e8031297771b89dae9e36a29
  content_type: application/pdf
  creator: dernst
  date_created: 2022-03-07T07:55:23Z
  date_updated: 2022-03-07T07:55:23Z
  file_id: '10831'
  file_name: 2022_Cell_Yanagida.pdf
  file_size: 8478995
  relation: main_file
  success: 1
file_date_updated: 2022-03-07T07:55:23Z
fulldoi: https://doi.org/10.1016/j.cell.2022.01.022
has_accepted_license: '1'
intvolume: '       185'
isi: 1
issue: '5'
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
page: 777-793.e20
pmid: 1
project:
- _id: 05943252-7A3F-11EA-A408-12923DDC885E
  call_identifier: H2020
  grant_number: '851288'
  name: Design Principles of Branching Morphogenesis
publication: Cell
publication_identifier:
  eissn:
  - 1097-4172
  issn:
  - 0092-8674
publication_status: published
publisher: Cell Press
quality_controlled: '1'
scopus_import: '1'
status: public
title: Cell surface fluctuations regulate early embryonic lineage sorting
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 185
year: '2022'
...
---
_id: '12209'
abstract:
- lang: eng
  text: Embryo development requires biochemical signalling to generate patterns of
    cell fates and active mechanical forces to drive tissue shape changes. However,
    how these processes are coordinated, and how tissue patterning is preserved despite
    the cellular flows occurring during morphogenesis, remains poorly understood.
    Gastrulation is a crucial embryonic stage that involves both patterning and internalization
    of the mesendoderm germ layer tissue. Here we show that, in zebrafish embryos,
    a gradient in Nodal signalling orchestrates pattern-preserving internalization
    movements by triggering a motility-driven unjamming transition. In addition to
    its role as a morphogen determining embryo patterning, graded Nodal signalling
    mechanically subdivides the mesendoderm into a small fraction of highly protrusive
    leader cells, able to autonomously internalize via local unjamming, and less protrusive
    followers, which need to be pulled inwards by the leaders. The Nodal gradient
    further enforces a code of preferential adhesion coupling leaders to their immediate
    followers, resulting in a collective and ordered mode of internalization that
    preserves mesendoderm patterning. Integrating this dual mechanical role of Nodal
    signalling into minimal active particle simulations quantitatively predicts both
    physiological and experimentally perturbed internalization movements. This provides
    a quantitative framework for how a morphogen-encoded unjamming transition can
    bidirectionally couple tissue mechanics with patterning during complex three-dimensional
    morphogenesis.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
acknowledgement: "We thank K. Sampath, A. Pauli and Y. Bellaїche for feedback on the
  manuscript. We also thank the members of the Heisenberg group, in particular A.
  Schauer and F. Nur Arslan, for help, technical advice and discussions, and the Bioimaging
  and Life Science facilities at IST\r\nAustria for continuous support. We thank C.
  Flandoli for the artwork in the figures. This work was supported by postdoctoral
  fellowships from EMBO (LTF-850-2017) and HFSP (LT000429/2018-L2) to D.P. and the
  European Union (European Research Council starting grant 851288 to É.H. and European
  Research Council advanced grant 742573 to C.-P.H.)."
article_processing_charge: No
article_type: original
author:
- first_name: Diana C
  full_name: Nunes Pinheiro, Diana C
  id: 2E839F16-F248-11E8-B48F-1D18A9856A87
  last_name: Nunes Pinheiro
  orcid: 0000-0003-4333-7503
- first_name: Roland
  full_name: Kardos, Roland
  id: 4039350E-F248-11E8-B48F-1D18A9856A87
  last_name: Kardos
- first_name: Edouard B
  full_name: Hannezo, Edouard B
  id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
  last_name: Hannezo
  orcid: 0000-0001-6005-1561
- first_name: Carl-Philipp J
  full_name: Heisenberg, Carl-Philipp J
  id: 39427864-F248-11E8-B48F-1D18A9856A87
  last_name: Heisenberg
  orcid: 0000-0002-0912-4566
citation:
  ama: Nunes Pinheiro DC, Kardos R, Hannezo EB, Heisenberg C-PJ. Morphogen gradient
    orchestrates pattern-preserving tissue morphogenesis via motility-driven unjamming.
    <i>Nature Physics</i>. 2022;18(12):1482-1493. doi:<a href="https://doi.org/10.1038/s41567-022-01787-6">10.1038/s41567-022-01787-6</a>
  apa: Nunes Pinheiro, D. C., Kardos, R., Hannezo, E. B., &#38; Heisenberg, C.-P.
    J. (2022). Morphogen gradient orchestrates pattern-preserving tissue morphogenesis
    via motility-driven unjamming. <i>Nature Physics</i>. Springer Nature. <a href="https://doi.org/10.1038/s41567-022-01787-6">https://doi.org/10.1038/s41567-022-01787-6</a>
  chicago: Nunes Pinheiro, Diana C, Roland Kardos, Edouard B Hannezo, and Carl-Philipp
    J Heisenberg. “Morphogen Gradient Orchestrates Pattern-Preserving Tissue Morphogenesis
    via Motility-Driven Unjamming.” <i>Nature Physics</i>. Springer Nature, 2022.
    <a href="https://doi.org/10.1038/s41567-022-01787-6">https://doi.org/10.1038/s41567-022-01787-6</a>.
  ieee: D. C. Nunes Pinheiro, R. Kardos, E. B. Hannezo, and C.-P. J. Heisenberg, “Morphogen
    gradient orchestrates pattern-preserving tissue morphogenesis via motility-driven
    unjamming,” <i>Nature Physics</i>, vol. 18, no. 12. Springer Nature, pp. 1482–1493,
    2022.
  ista: Nunes Pinheiro DC, Kardos R, Hannezo EB, Heisenberg C-PJ. 2022. Morphogen
    gradient orchestrates pattern-preserving tissue morphogenesis via motility-driven
    unjamming. Nature Physics. 18(12), 1482–1493.
  mla: Nunes Pinheiro, Diana C., et al. “Morphogen Gradient Orchestrates Pattern-Preserving
    Tissue Morphogenesis via Motility-Driven Unjamming.” <i>Nature Physics</i>, vol.
    18, no. 12, Springer Nature, 2022, pp. 1482–93, doi:<a href="https://doi.org/10.1038/s41567-022-01787-6">10.1038/s41567-022-01787-6</a>.
  short: D.C. Nunes Pinheiro, R. Kardos, E.B. Hannezo, C.-P.J. Heisenberg, Nature
    Physics 18 (2022) 1482–1493.
corr_author: '1'
date_created: 2023-01-16T09:45:19Z
date_published: 2022-12-01T00:00:00Z
date_updated: 2025-04-14T07:46:59Z
day: '01'
ddc:
- '570'
department:
- _id: CaHe
- _id: EdHa
doi: 10.1038/s41567-022-01787-6
ec_funded: 1
external_id:
  isi:
  - '000871319900002'
file:
- access_level: open_access
  checksum: c86a8e8d80d1bfc46d56a01e88a2526a
  content_type: application/pdf
  creator: dernst
  date_created: 2023-01-27T07:32:01Z
  date_updated: 2023-01-27T07:32:01Z
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  file_size: 36703569
  relation: main_file
  success: 1
file_date_updated: 2023-01-27T07:32:01Z
fulldoi: https://doi.org/10.1038/s41567-022-01787-6
has_accepted_license: '1'
intvolume: '        18'
isi: 1
issue: '12'
keyword:
- General Physics and Astronomy
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
page: 1482-1493
project:
- _id: 26520D1E-B435-11E9-9278-68D0E5697425
  grant_number: ALTF 850-2017
  name: Coordination of mesendoderm cell fate specification and internalization during
    zebrafish gastrulation
- _id: 26520D1E-B435-11E9-9278-68D0E5697425
  grant_number: ALTF 850-2017
  name: Coordination of mesendoderm cell fate specification and internalization during
    zebrafish gastrulation
- _id: 05943252-7A3F-11EA-A408-12923DDC885E
  call_identifier: H2020
  grant_number: '851288'
  name: Design Principles of Branching Morphogenesis
- _id: 260F1432-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '742573'
  name: Interaction and feedback between cell mechanics and fate specification in
    vertebrate gastrulation
publication: Nature Physics
publication_identifier:
  eissn:
  - 1745-2481
  issn:
  - 1745-2473
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Morphogen gradient orchestrates pattern-preserving tissue morphogenesis via
  motility-driven unjamming
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 18
year: '2022'
...
---
_id: '12217'
abstract:
- lang: eng
  text: The development dynamics and self-organization of glandular branched epithelia
    is of utmost importance for our understanding of diverse processes ranging from
    normal tissue growth to the growth of cancerous tissues. Using single primary
    murine pancreatic ductal adenocarcinoma (PDAC) cells embedded in a collagen matrix
    and adapted media supplementation, we generate organoids that self-organize into
    highly branched structures displaying a seamless lumen connecting terminal end
    buds, replicating in vivo PDAC architecture. We identify distinct morphogenesis
    phases, each characterized by a unique pattern of cell invasion, matrix deformation,
    protein expression, and respective molecular dependencies. We propose a minimal
    theoretical model of a branching and proliferating tissue, capturing the dynamics
    of the first phases. Observing the interaction of morphogenesis, mechanical environment
    and gene expression in vitro sets a benchmark for the understanding of self-organization
    processes governing complex organoid structure formation processes and branching
    morphogenesis.
acknowledgement: "A.R.B. acknowledges the financial support of the European Research
  Council (ERC) through the funding of the grant Principles of Integrin Mechanics
  and Adhesion (PoINT) and the German Research Foundation (DFG, SFB 1032, project
  ID 201269156). E.H. was supported by the European Union (European Research Council
  Starting Grant 851288). D.S., M.R., and R.R. acknowledge the support by the German
  Research Foundation (DFG, SFB1321 Modeling and Targeting Pancreatic Cancer, Project
  S01, project ID 329628492). C.S. and M.R. acknowledge the support by the German
  Research Foundation (DFG, SFB1321 Modeling and Targeting Pancreatic Cancer, Project
  12, project ID 329628492). M.R. was supported by the German Research Foundation
  (DFG RE 3723/4-1). A.P. and M.R. were supported by the German Cancer Aid (Max-Eder
  Program 111273 and 70114328).\r\nOpen Access funding enabled and organized by Projekt
  DEAL."
article_number: '5219'
article_processing_charge: No
article_type: original
author:
- first_name: S.
  full_name: Randriamanantsoa, S.
  last_name: Randriamanantsoa
- first_name: A.
  full_name: Papargyriou, A.
  last_name: Papargyriou
- first_name: H. C.
  full_name: Maurer, H. C.
  last_name: Maurer
- first_name: K.
  full_name: Peschke, K.
  last_name: Peschke
- first_name: M.
  full_name: Schuster, M.
  last_name: Schuster
- first_name: G.
  full_name: Zecchin, G.
  last_name: Zecchin
- first_name: K.
  full_name: Steiger, K.
  last_name: Steiger
- first_name: R.
  full_name: Öllinger, R.
  last_name: Öllinger
- first_name: D.
  full_name: Saur, D.
  last_name: Saur
- first_name: C.
  full_name: Scheel, C.
  last_name: Scheel
- first_name: R.
  full_name: Rad, R.
  last_name: Rad
- first_name: Edouard B
  full_name: Hannezo, Edouard B
  id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
  last_name: Hannezo
  orcid: 0000-0001-6005-1561
- first_name: M.
  full_name: Reichert, M.
  last_name: Reichert
- first_name: A. R.
  full_name: Bausch, A. R.
  last_name: Bausch
citation:
  ama: Randriamanantsoa S, Papargyriou A, Maurer HC, et al. Spatiotemporal dynamics
    of self-organized branching in pancreas-derived organoids. <i>Nature Communications</i>.
    2022;13. doi:<a href="https://doi.org/10.1038/s41467-022-32806-y">10.1038/s41467-022-32806-y</a>
  apa: Randriamanantsoa, S., Papargyriou, A., Maurer, H. C., Peschke, K., Schuster,
    M., Zecchin, G., … Bausch, A. R. (2022). Spatiotemporal dynamics of self-organized
    branching in pancreas-derived organoids. <i>Nature Communications</i>. Springer
    Nature. <a href="https://doi.org/10.1038/s41467-022-32806-y">https://doi.org/10.1038/s41467-022-32806-y</a>
  chicago: Randriamanantsoa, S., A. Papargyriou, H. C. Maurer, K. Peschke, M. Schuster,
    G. Zecchin, K. Steiger, et al. “Spatiotemporal Dynamics of Self-Organized Branching
    in Pancreas-Derived Organoids.” <i>Nature Communications</i>. Springer Nature,
    2022. <a href="https://doi.org/10.1038/s41467-022-32806-y">https://doi.org/10.1038/s41467-022-32806-y</a>.
  ieee: S. Randriamanantsoa <i>et al.</i>, “Spatiotemporal dynamics of self-organized
    branching in pancreas-derived organoids,” <i>Nature Communications</i>, vol. 13.
    Springer Nature, 2022.
  ista: Randriamanantsoa S, Papargyriou A, Maurer HC, Peschke K, Schuster M, Zecchin
    G, Steiger K, Öllinger R, Saur D, Scheel C, Rad R, Hannezo EB, Reichert M, Bausch
    AR. 2022. Spatiotemporal dynamics of self-organized branching in pancreas-derived
    organoids. Nature Communications. 13, 5219.
  mla: Randriamanantsoa, S., et al. “Spatiotemporal Dynamics of Self-Organized Branching
    in Pancreas-Derived Organoids.” <i>Nature Communications</i>, vol. 13, 5219, Springer
    Nature, 2022, doi:<a href="https://doi.org/10.1038/s41467-022-32806-y">10.1038/s41467-022-32806-y</a>.
  short: S. Randriamanantsoa, A. Papargyriou, H.C. Maurer, K. Peschke, M. Schuster,
    G. Zecchin, K. Steiger, R. Öllinger, D. Saur, C. Scheel, R. Rad, E.B. Hannezo,
    M. Reichert, A.R. Bausch, Nature Communications 13 (2022).
date_created: 2023-01-16T09:46:53Z
date_published: 2022-09-05T00:00:00Z
date_updated: 2025-06-11T13:53:55Z
day: '05'
ddc:
- '570'
department:
- _id: EdHa
doi: 10.1038/s41467-022-32806-y
ec_funded: 1
external_id:
  isi:
  - '000850348400025'
  pmid:
  - '36064947'
file:
- access_level: open_access
  checksum: 295261b5172274fd5b8f85a6a6058828
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  creator: dernst
  date_created: 2023-01-27T08:14:48Z
  date_updated: 2023-01-27T08:14:48Z
  file_id: '12416'
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file_date_updated: 2023-01-27T08:14:48Z
fulldoi: https://doi.org/10.1038/s41467-022-32806-y
has_accepted_license: '1'
intvolume: '        13'
isi: 1
keyword:
- General Physics and Astronomy
- General Biochemistry
- Genetics and Molecular Biology
- General Chemistry
- Multidisciplinary
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 05943252-7A3F-11EA-A408-12923DDC885E
  call_identifier: H2020
  grant_number: '851288'
  name: Design Principles of Branching Morphogenesis
publication: Nature Communications
publication_identifier:
  issn:
  - 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
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    status: public
scopus_import: '1'
status: public
title: Spatiotemporal dynamics of self-organized branching in pancreas-derived organoids
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 13
year: '2022'
...
---
_id: '12253'
abstract:
- lang: eng
  text: The sculpting of germ layers during gastrulation relies on the coordinated
    migration of progenitor cells, yet the cues controlling these long-range directed
    movements remain largely unknown. While directional migration often relies on
    a chemokine gradient generated from a localized source, we find that zebrafish
    ventrolateral mesoderm is guided by a self-generated gradient of the initially
    uniformly expressed and secreted protein Toddler/ELABELA/Apela. We show that the
    Apelin receptor, which is specifically expressed in mesodermal cells, has a dual
    role during gastrulation, acting as a scavenger receptor to generate a Toddler
    gradient, and as a chemokine receptor to sense this guidance cue. Thus, we uncover
    a single receptor–based self-generated gradient as the enigmatic guidance cue
    that can robustly steer the directional migration of mesoderm through the complex
    and continuously changing environment of the gastrulating embryo.
acknowledgement: 'We thank K. Aumayer and the team of the biooptics facility at the
  Vienna Biocenter, particularly P. Pasierbek and T. Müller, for support with microscopy;
  K. Panser, C. Pribitzer, and the animal facility personnel for taking care of zebrafish;
  M. Binner and A. Bandura for help with genotyping; M. Codina Tobias for help with
  establishing the conditions for the Toddler overexpression compensation experiment;
  T. Lubiana Alves for sharing the code for scRNA-Seq analyses; the Heisenberg laboratory,
  particularly D. Pinheiro, for joint laboratory meetings, discussions on the project,
  and providing the tg(gsc:CAAX-GFP) fish line; the Raz laboratory for providing the
  Lifeact-GFP plasmid; A. Andersen, A. Schier, C.-P. Heisenberg, and E. Tanaka for
  comments on the manuscript; and the entire Pauli laboratory, particularly K. Gert
  and V. Deneke, for valuable discussions and feedback on the manuscript. Funding:
  Work in A.P.’s laboratory has been supported by the IMP, which receives institutional
  funding from Boehringer Ingelheim and the Austrian Research Promotion Agency (Headquarter
  grant FFG-852936), as well as the FWF START program (Y 1031-B28 to A.P.), the Human
  Frontier Science Program (HFSP) Career Development Award (CDA00066/2015 to A.P.)
  and Young Investigator Grant (RGY0079/2020 to A.P.), the SFB RNA-Deco (project number
  F 80 to A.P.), a Whitman Center Fellowship from the Marine Biological Laboratory
  (to A.P.), and EMBO-YIP funds (to A.P.). This work was supported by the European
  Union (European Research Council Starting Grant 851288 to E.H.). For the purpose
  of Open Access, the authors have applied a CC BY public copyright license to any
  Author Accepted Manuscript (AAM) version arising from this submission.'
article_number: eadd2488
article_processing_charge: No
article_type: original
author:
- first_name: Jessica
  full_name: Stock, Jessica
  last_name: Stock
- first_name: Tomas
  full_name: Kazmar, Tomas
  last_name: Kazmar
- first_name: Friederike
  full_name: Schlumm, Friederike
  last_name: Schlumm
- first_name: Edouard B
  full_name: Hannezo, Edouard B
  id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
  last_name: Hannezo
  orcid: 0000-0001-6005-1561
- first_name: Andrea
  full_name: Pauli, Andrea
  last_name: Pauli
citation:
  ama: Stock J, Kazmar T, Schlumm F, Hannezo EB, Pauli A. A self-generated Toddler
    gradient guides mesodermal cell migration. <i>Science Advances</i>. 2022;8(37).
    doi:<a href="https://doi.org/10.1126/sciadv.add2488">10.1126/sciadv.add2488</a>
  apa: Stock, J., Kazmar, T., Schlumm, F., Hannezo, E. B., &#38; Pauli, A. (2022).
    A self-generated Toddler gradient guides mesodermal cell migration. <i>Science
    Advances</i>. American Association for the Advancement of Science. <a href="https://doi.org/10.1126/sciadv.add2488">https://doi.org/10.1126/sciadv.add2488</a>
  chicago: Stock, Jessica, Tomas Kazmar, Friederike Schlumm, Edouard B Hannezo, and
    Andrea Pauli. “A Self-Generated Toddler Gradient Guides Mesodermal Cell Migration.”
    <i>Science Advances</i>. American Association for the Advancement of Science,
    2022. <a href="https://doi.org/10.1126/sciadv.add2488">https://doi.org/10.1126/sciadv.add2488</a>.
  ieee: J. Stock, T. Kazmar, F. Schlumm, E. B. Hannezo, and A. Pauli, “A self-generated
    Toddler gradient guides mesodermal cell migration,” <i>Science Advances</i>, vol.
    8, no. 37. American Association for the Advancement of Science, 2022.
  ista: Stock J, Kazmar T, Schlumm F, Hannezo EB, Pauli A. 2022. A self-generated
    Toddler gradient guides mesodermal cell migration. Science Advances. 8(37), eadd2488.
  mla: Stock, Jessica, et al. “A Self-Generated Toddler Gradient Guides Mesodermal
    Cell Migration.” <i>Science Advances</i>, vol. 8, no. 37, eadd2488, American Association
    for the Advancement of Science, 2022, doi:<a href="https://doi.org/10.1126/sciadv.add2488">10.1126/sciadv.add2488</a>.
  short: J. Stock, T. Kazmar, F. Schlumm, E.B. Hannezo, A. Pauli, Science Advances
    8 (2022).
date_created: 2023-01-16T09:57:10Z
date_published: 2022-09-14T00:00:00Z
date_updated: 2025-04-14T07:52:27Z
day: '14'
ddc:
- '570'
department:
- _id: EdHa
doi: 10.1126/sciadv.add2488
ec_funded: 1
external_id:
  isi:
  - '000888875000009'
  pmid:
  - '36103529'
file:
- access_level: open_access
  checksum: f59cdb824e5d4221045def81f46f6c65
  content_type: application/pdf
  creator: dernst
  date_created: 2023-01-30T09:27:49Z
  date_updated: 2023-01-30T09:27:49Z
  file_id: '12444'
  file_name: 2022_ScienceAdvances_Stock.pdf
  file_size: 1636732
  relation: main_file
  success: 1
file_date_updated: 2023-01-30T09:27:49Z
fulldoi: https://doi.org/10.1126/sciadv.add2488
has_accepted_license: '1'
intvolume: '         8'
isi: 1
issue: '37'
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 05943252-7A3F-11EA-A408-12923DDC885E
  call_identifier: H2020
  grant_number: '851288'
  name: Design Principles of Branching Morphogenesis
publication: Science Advances
publication_identifier:
  issn:
  - 2375-2548
publication_status: published
publisher: American Association for the Advancement of Science
quality_controlled: '1'
scopus_import: '1'
status: public
title: A self-generated Toddler gradient guides mesodermal cell migration
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 8
year: '2022'
...
---
_id: '12274'
abstract:
- lang: eng
  text: The morphology and functionality of the epithelial lining differ along the
    intestinal tract, but tissue renewal at all sites is driven by stem cells at the
    base of crypts1,2,3. Whether stem cell numbers and behaviour vary at different
    sites is unknown. Here we show using intravital microscopy that, despite similarities
    in the number and distribution of proliferative cells with an Lgr5 signature in
    mice, small intestinal crypts contain twice as many effective stem cells as large
    intestinal crypts. We find that, although passively displaced by a conveyor-belt-like
    upward movement, small intestinal cells positioned away from the crypt base can
    function as long-term effective stem cells owing to Wnt-dependent retrograde cellular
    movement. By contrast, the near absence of retrograde movement in the large intestine
    restricts cell repositioning, leading to a reduction in effective stem cell number.
    Moreover, after suppression of the retrograde movement in the small intestine,
    the number of effective stem cells is reduced, and the rate of monoclonal conversion
    of crypts is accelerated. Together, these results show that the number of effective
    stem cells is determined by active retrograde movement, revealing a new channel
    of stem cell regulation that can be experimentally and pharmacologically manipulated.
acknowledgement: We thank the members of the van Rheenen laboratory for reading the
  manuscript, and the members of the bioimaging, FACS and animal facility of the NKI
  for experimental support. We acknowledge the staff at the MedH Flow Cytometry core
  facility, Karolinska Institutet, and LCI facility/Nikon Center of Excellence, Karolinska
  Institutet. This work was financially supported by the Netherlands Organization
  of Scientific Research NWO (Veni grant 863.15.011 to S.I.J.E. and Vici grant 09150182110004
  to J.v.R.) and the CancerGenomics.nl (Netherlands Organisation for Scientific Research)
  program (to J.v.R.) the Doctor Josef Steiner Foundation (to J.v.R). B.D.S. acknowledges
  funding from the Royal Society E.P. Abraham Research Professorship (RP\R1\180165)
  and the Wellcome Trust (098357/Z/12/Z and 219478/Z/19/Z). B.C.-M. acknowledges the
  support of the field of excellence ‘Complexity of life in basic research and innovation’
  of the University of Graz. O.J.S. and their laboratory acknowledge CRUK core funding
  to the CRUK Beatson Institute (A17196 and A31287) and CRUK core funding to the Sansom
  laboratory (A21139). P.K. and their laboratory are supported by grants from the
  Swedish Research Council (2018-03078), Cancerfonden (190634), Academy of Finland
  Centre of Excellence (266869, 304591 and 320185) and the Jane and Aatos Erkko Foundation.
  P.L. has received funding from the European Research Council (ERC) under the European
  Union’s Horizon 2020 research and innovation programme (grant agreement no. 758617).
  E.H. acknowledges funding from the European Research Council (ERC) under the European
  Union’s Horizon 2020 research and innovation programme (grant agreement no. 851288).
article_processing_charge: No
article_type: original
author:
- first_name: Maria
  full_name: Azkanaz, Maria
  last_name: Azkanaz
- first_name: Bernat
  full_name: Corominas-Murtra, Bernat
  id: 43BE2298-F248-11E8-B48F-1D18A9856A87
  last_name: Corominas-Murtra
  orcid: 0000-0001-9806-5643
- first_name: Saskia I. J.
  full_name: Ellenbroek, Saskia I. J.
  last_name: Ellenbroek
- first_name: Lotte
  full_name: Bruens, Lotte
  last_name: Bruens
- first_name: Anna T.
  full_name: Webb, Anna T.
  last_name: Webb
- first_name: Dimitrios
  full_name: Laskaris, Dimitrios
  last_name: Laskaris
- first_name: Koen C.
  full_name: Oost, Koen C.
  last_name: Oost
- first_name: Simona J. A.
  full_name: Lafirenze, Simona J. A.
  last_name: Lafirenze
- first_name: Karl
  full_name: Annusver, Karl
  last_name: Annusver
- first_name: Hendrik A.
  full_name: Messal, Hendrik A.
  last_name: Messal
- first_name: Sharif
  full_name: Iqbal, Sharif
  last_name: Iqbal
- first_name: Dustin J.
  full_name: Flanagan, Dustin J.
  last_name: Flanagan
- first_name: David J.
  full_name: Huels, David J.
  last_name: Huels
- first_name: Felipe
  full_name: Rojas-Rodríguez, Felipe
  last_name: Rojas-Rodríguez
- first_name: Miguel
  full_name: Vizoso, Miguel
  last_name: Vizoso
- first_name: Maria
  full_name: Kasper, Maria
  last_name: Kasper
- first_name: Owen J.
  full_name: Sansom, Owen J.
  last_name: Sansom
- first_name: Hugo J.
  full_name: Snippert, Hugo J.
  last_name: Snippert
- first_name: Prisca
  full_name: Liberali, Prisca
  last_name: Liberali
- first_name: Benjamin D.
  full_name: Simons, Benjamin D.
  last_name: Simons
- first_name: Pekka
  full_name: Katajisto, Pekka
  last_name: Katajisto
- first_name: Edouard B
  full_name: Hannezo, Edouard B
  id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
  last_name: Hannezo
  orcid: 0000-0001-6005-1561
- first_name: Jacco
  full_name: van Rheenen, Jacco
  last_name: van Rheenen
citation:
  ama: Azkanaz M, Corominas-Murtra B, Ellenbroek SIJ, et al. Retrograde movements
    determine effective stem cell numbers in the intestine. <i>Nature</i>. 2022;607(7919):548-554.
    doi:<a href="https://doi.org/10.1038/s41586-022-04962-0">10.1038/s41586-022-04962-0</a>
  apa: Azkanaz, M., Corominas-Murtra, B., Ellenbroek, S. I. J., Bruens, L., Webb,
    A. T., Laskaris, D., … van Rheenen, J. (2022). Retrograde movements determine
    effective stem cell numbers in the intestine. <i>Nature</i>. Springer Nature.
    <a href="https://doi.org/10.1038/s41586-022-04962-0">https://doi.org/10.1038/s41586-022-04962-0</a>
  chicago: Azkanaz, Maria, Bernat Corominas-Murtra, Saskia I. J. Ellenbroek, Lotte
    Bruens, Anna T. Webb, Dimitrios Laskaris, Koen C. Oost, et al. “Retrograde Movements
    Determine Effective Stem Cell Numbers in the Intestine.” <i>Nature</i>. Springer
    Nature, 2022. <a href="https://doi.org/10.1038/s41586-022-04962-0">https://doi.org/10.1038/s41586-022-04962-0</a>.
  ieee: M. Azkanaz <i>et al.</i>, “Retrograde movements determine effective stem cell
    numbers in the intestine,” <i>Nature</i>, vol. 607, no. 7919. Springer Nature,
    pp. 548–554, 2022.
  ista: Azkanaz M, Corominas-Murtra B, Ellenbroek SIJ, Bruens L, Webb AT, Laskaris
    D, Oost KC, Lafirenze SJA, Annusver K, Messal HA, Iqbal S, Flanagan DJ, Huels
    DJ, Rojas-Rodríguez F, Vizoso M, Kasper M, Sansom OJ, Snippert HJ, Liberali P,
    Simons BD, Katajisto P, Hannezo EB, van Rheenen J. 2022. Retrograde movements
    determine effective stem cell numbers in the intestine. Nature. 607(7919), 548–554.
  mla: Azkanaz, Maria, et al. “Retrograde Movements Determine Effective Stem Cell
    Numbers in the Intestine.” <i>Nature</i>, vol. 607, no. 7919, Springer Nature,
    2022, pp. 548–54, doi:<a href="https://doi.org/10.1038/s41586-022-04962-0">10.1038/s41586-022-04962-0</a>.
  short: M. Azkanaz, B. Corominas-Murtra, S.I.J. Ellenbroek, L. Bruens, A.T. Webb,
    D. Laskaris, K.C. Oost, S.J.A. Lafirenze, K. Annusver, H.A. Messal, S. Iqbal,
    D.J. Flanagan, D.J. Huels, F. Rojas-Rodríguez, M. Vizoso, M. Kasper, O.J. Sansom,
    H.J. Snippert, P. Liberali, B.D. Simons, P. Katajisto, E.B. Hannezo, J. van Rheenen,
    Nature 607 (2022) 548–554.
corr_author: '1'
date_created: 2023-01-16T10:01:29Z
date_published: 2022-07-13T00:00:00Z
date_updated: 2025-04-14T07:52:27Z
day: '13'
department:
- _id: EdHa
doi: 10.1038/s41586-022-04962-0
ec_funded: 1
external_id:
  isi:
  - '000824430000004'
  pmid:
  - '35831497'
fulldoi: https://doi.org/10.1038/s41586-022-04962-0
intvolume: '       607'
isi: 1
issue: '7919'
keyword:
- Multidisciplinary
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://helda.helsinki.fi/items/94433455-4854-45c0-9de8-7326caea8780
month: '07'
oa: 1
oa_version: Submitted Version
page: 548-554
pmid: 1
project:
- _id: 05943252-7A3F-11EA-A408-12923DDC885E
  call_identifier: H2020
  grant_number: '851288'
  name: Design Principles of Branching Morphogenesis
publication: Nature
publication_identifier:
  eissn:
  - 1476-4687
  issn:
  - 0028-0836
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
  link:
  - relation: software
    url: https://github.com/JaccovanRheenenLab/Retrograde_movement_Azkanaz_Nature_2022
scopus_import: '1'
status: public
title: Retrograde movements determine effective stem cell numbers in the intestine
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 607
year: '2022'
...
---
_id: '12277'
abstract:
- lang: eng
  text: Cell migration in confining physiological environments relies on the concerted
    dynamics of several cellular components, including protrusions, adhesions with
    the environment, and the cell nucleus. However, it remains poorly understood how
    the dynamic interplay of these components and the cell polarity determine the
    emergent migration behavior at the cellular scale. Here, we combine data-driven
    inference with a mechanistic bottom-up approach to develop a model for protrusion
    and polarity dynamics in confined cell migration, revealing how the cellular dynamics
    adapt to confining geometries. Specifically, we use experimental data of joint
    protrusion-nucleus migration trajectories of cells on confining micropatterns
    to systematically determine a mechanistic model linking the stochastic dynamics
    of cell polarity, protrusions, and nucleus. This model indicates that the cellular
    dynamics adapt to confining constrictions through a switch in the polarity dynamics
    from a negative to a positive self-reinforcing feedback loop. Our model further
    reveals how this feedback loop leads to stereotypical cycles of protrusion-nucleus
    dynamics that drive the migration of the cell through constrictions. These cycles
    are disrupted upon perturbation of cytoskeletal components, indicating that the
    positive feedback is controlled by cellular migration mechanisms. Our data-driven
    theoretical approach therefore identifies polarity feedback adaptation as a key
    mechanism in confined cell migration.
acknowledgement: "We thank Grzegorz Gradziuk, StevenRiedijk, Janni Harju, and M. R.
  Schnucki for helpful discussions, and Andriy Goychuk for advice on the image segmentation.
  This project\r\nwas funded by the Deutsche Forschungsgemeinschaft (DFG, German Research
  Foundation), Project No. 201269156—SFB 1032 (Projects B01 and B12). D. B. B. is
  supported by the NOMIS Foundation and in part by a DFG fellowship within the Graduate
  School of Quantitative Biosciences Munich (QBM), as well as by the Joachim Herz
  Stiftung."
article_number: '031041'
article_processing_charge: No
article_type: original
arxiv: 1
author:
- first_name: David
  full_name: Brückner, David
  id: e1e86031-6537-11eb-953a-f7ab92be508d
  last_name: Brückner
  orcid: 0000-0001-7205-2975
- first_name: Matthew
  full_name: Schmitt, Matthew
  last_name: Schmitt
- first_name: Alexandra
  full_name: Fink, Alexandra
  last_name: Fink
- first_name: Georg
  full_name: Ladurner, Georg
  last_name: Ladurner
- first_name: Johannes
  full_name: Flommersfeld, Johannes
  last_name: Flommersfeld
- first_name: Nicolas
  full_name: Arlt, Nicolas
  last_name: Arlt
- first_name: Edouard B
  full_name: Hannezo, Edouard B
  id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
  last_name: Hannezo
  orcid: 0000-0001-6005-1561
- first_name: Joachim O.
  full_name: Rädler, Joachim O.
  last_name: Rädler
- first_name: Chase P.
  full_name: Broedersz, Chase P.
  last_name: Broedersz
citation:
  ama: Brückner D, Schmitt M, Fink A, et al. Geometry adaptation of protrusion and
    polarity dynamics in confined cell migration. <i>Physical Review X</i>. 2022;12(3).
    doi:<a href="https://doi.org/10.1103/physrevx.12.031041">10.1103/physrevx.12.031041</a>
  apa: Brückner, D., Schmitt, M., Fink, A., Ladurner, G., Flommersfeld, J., Arlt,
    N., … Broedersz, C. P. (2022). Geometry adaptation of protrusion and polarity
    dynamics in confined cell migration. <i>Physical Review X</i>. American Physical
    Society. <a href="https://doi.org/10.1103/physrevx.12.031041">https://doi.org/10.1103/physrevx.12.031041</a>
  chicago: Brückner, David, Matthew Schmitt, Alexandra Fink, Georg Ladurner, Johannes
    Flommersfeld, Nicolas Arlt, Edouard B Hannezo, Joachim O. Rädler, and Chase P.
    Broedersz. “Geometry Adaptation of Protrusion and Polarity Dynamics in Confined
    Cell Migration.” <i>Physical Review X</i>. American Physical Society, 2022. <a
    href="https://doi.org/10.1103/physrevx.12.031041">https://doi.org/10.1103/physrevx.12.031041</a>.
  ieee: D. Brückner <i>et al.</i>, “Geometry adaptation of protrusion and polarity
    dynamics in confined cell migration,” <i>Physical Review X</i>, vol. 12, no. 3.
    American Physical Society, 2022.
  ista: Brückner D, Schmitt M, Fink A, Ladurner G, Flommersfeld J, Arlt N, Hannezo
    EB, Rädler JO, Broedersz CP. 2022. Geometry adaptation of protrusion and polarity
    dynamics in confined cell migration. Physical Review X. 12(3), 031041.
  mla: Brückner, David, et al. “Geometry Adaptation of Protrusion and Polarity Dynamics
    in Confined Cell Migration.” <i>Physical Review X</i>, vol. 12, no. 3, 031041,
    American Physical Society, 2022, doi:<a href="https://doi.org/10.1103/physrevx.12.031041">10.1103/physrevx.12.031041</a>.
  short: D. Brückner, M. Schmitt, A. Fink, G. Ladurner, J. Flommersfeld, N. Arlt,
    E.B. Hannezo, J.O. Rädler, C.P. Broedersz, Physical Review X 12 (2022).
date_created: 2023-01-16T10:02:06Z
date_published: 2022-09-20T00:00:00Z
date_updated: 2023-08-04T10:25:49Z
day: '20'
ddc:
- '530'
- '570'
department:
- _id: EdHa
doi: 10.1103/physrevx.12.031041
external_id:
  arxiv:
  - '2106.01014'
  isi:
  - '000861534700001'
file:
- access_level: open_access
  checksum: 40a8fbc3663bf07b37cb80020974d40d
  content_type: application/pdf
  creator: dernst
  date_created: 2023-01-30T11:07:27Z
  date_updated: 2023-01-30T11:07:27Z
  file_id: '12458'
  file_name: 2022_PhysicalReviewX_Brueckner.pdf
  file_size: 4686804
  relation: main_file
  success: 1
file_date_updated: 2023-01-30T11:07:27Z
fulldoi: https://doi.org/10.1103/physrevx.12.031041
has_accepted_license: '1'
intvolume: '        12'
isi: 1
issue: '3'
keyword:
- General Physics and Astronomy
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
publication: Physical Review X
publication_identifier:
  issn:
  - 2160-3308
publication_status: published
publisher: American Physical Society
quality_controlled: '1'
scopus_import: '1'
status: public
title: Geometry adaptation of protrusion and polarity dynamics in confined cell migration
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 12
year: '2022'
...
---
_id: '10530'
abstract:
- lang: eng
  text: "Cell dispersion from a confined area is fundamental in a number of biological
    processes,\r\nincluding cancer metastasis. To date, a quantitative understanding
    of the interplay of single\r\ncell motility, cell proliferation, and intercellular
    contacts remains elusive. In particular, the role\r\nof E- and N-Cadherin junctions,
    central components of intercellular contacts, is still\r\ncontroversial. Combining
    theoretical modeling with in vitro observations, we investigate the\r\ncollective
    spreading behavior of colonies of human cancer cells (T24). The spreading of these\r\ncolonies
    is driven by stochastic single-cell migration with frequent transient cell-cell
    contacts.\r\nWe find that inhibition of E- and N-Cadherin junctions decreases
    colony spreading and average\r\nspreading velocities, without affecting the strength
    of correlations in spreading velocities of\r\nneighboring cells. Based on a biophysical
    simulation model for cell migration, we show that the\r\nbehavioral changes upon
    disruption of these junctions can be explained by reduced repulsive\r\nexcluded
    volume interactions between cells. This suggests that in cancer cell migration,\r\ncadherin-based
    intercellular contacts sharpen cell boundaries leading to repulsive rather than\r\ncohesive
    interactions between cells, thereby promoting efficient cell spreading during
    collective\r\nmigration.\r\n"
acknowledgement: Funded by the Deutsche Forschungsgemeinschaft (DFG, German Research
  Foundation) - Project-ID 201269156 - SFB 1032 (Projects B8 and B12). D.B.B. is supported
  in part by a DFG fellowship within the Graduate School of Quantitative Biosciences
  Munich (QBM) and by the Joachim Herz Stiftung.
article_processing_charge: No
article_type: original
author:
- first_name: Themistoklis
  full_name: Zisis, Themistoklis
  last_name: Zisis
- first_name: David
  full_name: Brückner, David
  id: e1e86031-6537-11eb-953a-f7ab92be508d
  last_name: Brückner
  orcid: 0000-0001-7205-2975
- first_name: Tom
  full_name: Brandstätter, Tom
  last_name: Brandstätter
- first_name: Wei Xiong
  full_name: Siow, Wei Xiong
  last_name: Siow
- first_name: Joseph
  full_name: d’Alessandro, Joseph
  last_name: d’Alessandro
- first_name: Angelika M.
  full_name: Vollmar, Angelika M.
  last_name: Vollmar
- first_name: Chase P.
  full_name: Broedersz, Chase P.
  last_name: Broedersz
- first_name: Stefan
  full_name: Zahler, Stefan
  last_name: Zahler
citation:
  ama: Zisis T, Brückner D, Brandstätter T, et al. Disentangling cadherin-mediated
    cell-cell interactions in collective cancer cell migration. <i>Biophysical Journal</i>.
    2022;121(1):P44-60. doi:<a href="https://doi.org/10.1016/j.bpj.2021.12.006">10.1016/j.bpj.2021.12.006</a>
  apa: Zisis, T., Brückner, D., Brandstätter, T., Siow, W. X., d’Alessandro, J., Vollmar,
    A. M., … Zahler, S. (2022). Disentangling cadherin-mediated cell-cell interactions
    in collective cancer cell migration. <i>Biophysical Journal</i>. Elsevier. <a
    href="https://doi.org/10.1016/j.bpj.2021.12.006">https://doi.org/10.1016/j.bpj.2021.12.006</a>
  chicago: Zisis, Themistoklis, David Brückner, Tom Brandstätter, Wei Xiong Siow,
    Joseph d’Alessandro, Angelika M. Vollmar, Chase P. Broedersz, and Stefan Zahler.
    “Disentangling Cadherin-Mediated Cell-Cell Interactions in Collective Cancer Cell
    Migration.” <i>Biophysical Journal</i>. Elsevier, 2022. <a href="https://doi.org/10.1016/j.bpj.2021.12.006">https://doi.org/10.1016/j.bpj.2021.12.006</a>.
  ieee: T. Zisis <i>et al.</i>, “Disentangling cadherin-mediated cell-cell interactions
    in collective cancer cell migration,” <i>Biophysical Journal</i>, vol. 121, no.
    1. Elsevier, pp. P44-60, 2022.
  ista: Zisis T, Brückner D, Brandstätter T, Siow WX, d’Alessandro J, Vollmar AM,
    Broedersz CP, Zahler S. 2022. Disentangling cadherin-mediated cell-cell interactions
    in collective cancer cell migration. Biophysical Journal. 121(1), P44-60.
  mla: Zisis, Themistoklis, et al. “Disentangling Cadherin-Mediated Cell-Cell Interactions
    in Collective Cancer Cell Migration.” <i>Biophysical Journal</i>, vol. 121, no.
    1, Elsevier, 2022, pp. P44-60, doi:<a href="https://doi.org/10.1016/j.bpj.2021.12.006">10.1016/j.bpj.2021.12.006</a>.
  short: T. Zisis, D. Brückner, T. Brandstätter, W.X. Siow, J. d’Alessandro, A.M.
    Vollmar, C.P. Broedersz, S. Zahler, Biophysical Journal 121 (2022) P44-60.
date_created: 2021-12-10T09:48:19Z
date_published: 2022-01-04T00:00:00Z
date_updated: 2025-06-11T13:59:29Z
day: '04'
ddc:
- '570'
department:
- _id: EdHa
- _id: GaTk
doi: 10.1016/j.bpj.2021.12.006
external_id:
  isi:
  - '000740815400007'
  pmid:
  - '34890578'
file:
- access_level: open_access
  checksum: 1aa7c3478e0c8256b973b632efd1f6b4
  content_type: application/pdf
  creator: dernst
  date_created: 2022-07-29T10:17:10Z
  date_updated: 2022-07-29T10:17:10Z
  file_id: '11697'
  file_name: 2022_BiophysicalJour_Zisis.pdf
  file_size: 4475504
  relation: main_file
  success: 1
file_date_updated: 2022-07-29T10:17:10Z
fulldoi: https://doi.org/10.1016/j.bpj.2021.12.006
has_accepted_license: '1'
intvolume: '       121'
isi: 1
issue: '1'
keyword:
- Biophysics
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc-nd/4.0/
month: '01'
oa: 1
oa_version: Published Version
page: P44-60
pmid: 1
project:
- _id: 9B861AAC-BA93-11EA-9121-9846C619BF3A
  name: NOMIS Fellowship Program
publication: Biophysical Journal
publication_identifier:
  issn:
  - 0006-3495
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Disentangling cadherin-mediated cell-cell interactions in collective cancer
  cell migration
tmp:
  image: /images/cc_by_nc_nd.png
  legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
  name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
    (CC BY-NC-ND 4.0)
  short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 121
year: '2022'
...
---
_id: '10705'
abstract:
- lang: eng
  text: Although rigidity and jamming transitions have been widely studied in physics
    and material science, their importance in a number of biological processes, including
    embryo development, tissue homeostasis, wound healing, and disease progression,
    has only begun to be recognized in the past few years. The hypothesis that biological
    systems can undergo rigidity/jamming transitions is attractive, as it would allow
    these systems to change their material properties rapidly and strongly. However,
    whether such transitions indeed occur in biological systems, how they are being
    regulated, and what their physiological relevance might be, is still being debated.
    Here, we review theoretical and experimental advances from the past few years,
    focusing on the regulation and role of potential tissue rigidity transitions in
    different biological processes.
acknowledgement: We thank present and former members of the Heisenberg and Hannezo
  groups, in particular Bernat Corominas-Murtra and Nicoletta Petridou, for helpful
  discussions, and Claudia Flandoli for the artwork. We apologize for not being able
  to cite a number of highly relevant studies, to stay within the maximum allowed
  number of citations.
article_processing_charge: No
article_type: original
author:
- first_name: Edouard B
  full_name: Hannezo, Edouard B
  id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
  last_name: Hannezo
  orcid: 0000-0001-6005-1561
- first_name: Carl-Philipp J
  full_name: Heisenberg, Carl-Philipp J
  id: 39427864-F248-11E8-B48F-1D18A9856A87
  last_name: Heisenberg
  orcid: 0000-0002-0912-4566
citation:
  ama: Hannezo EB, Heisenberg C-PJ. Rigidity transitions in development and disease.
    <i>Trends in Cell Biology</i>. 2022;32(5):P433-444. doi:<a href="https://doi.org/10.1016/j.tcb.2021.12.006">10.1016/j.tcb.2021.12.006</a>
  apa: Hannezo, E. B., &#38; Heisenberg, C.-P. J. (2022). Rigidity transitions in
    development and disease. <i>Trends in Cell Biology</i>. Cell Press. <a href="https://doi.org/10.1016/j.tcb.2021.12.006">https://doi.org/10.1016/j.tcb.2021.12.006</a>
  chicago: Hannezo, Edouard B, and Carl-Philipp J Heisenberg. “Rigidity Transitions
    in Development and Disease.” <i>Trends in Cell Biology</i>. Cell Press, 2022.
    <a href="https://doi.org/10.1016/j.tcb.2021.12.006">https://doi.org/10.1016/j.tcb.2021.12.006</a>.
  ieee: E. B. Hannezo and C.-P. J. Heisenberg, “Rigidity transitions in development
    and disease,” <i>Trends in Cell Biology</i>, vol. 32, no. 5. Cell Press, pp. P433-444,
    2022.
  ista: Hannezo EB, Heisenberg C-PJ. 2022. Rigidity transitions in development and
    disease. Trends in Cell Biology. 32(5), P433-444.
  mla: Hannezo, Edouard B., and Carl-Philipp J. Heisenberg. “Rigidity Transitions
    in Development and Disease.” <i>Trends in Cell Biology</i>, vol. 32, no. 5, Cell
    Press, 2022, pp. P433-444, doi:<a href="https://doi.org/10.1016/j.tcb.2021.12.006">10.1016/j.tcb.2021.12.006</a>.
  short: E.B. Hannezo, C.-P.J. Heisenberg, Trends in Cell Biology 32 (2022) P433-444.
corr_author: '1'
date_created: 2022-01-30T23:01:34Z
date_published: 2022-05-01T00:00:00Z
date_updated: 2024-10-09T21:01:30Z
day: '01'
department:
- _id: EdHa
- _id: CaHe
doi: 10.1016/j.tcb.2021.12.006
external_id:
  isi:
  - '000795773900009'
  pmid:
  - '35058104'
fulldoi: https://doi.org/10.1016/j.tcb.2021.12.006
intvolume: '        32'
isi: 1
issue: '5'
language:
- iso: eng
month: '05'
oa_version: None
page: P433-444
pmid: 1
publication: Trends in Cell Biology
publication_identifier:
  eissn:
  - 1879-3088
  issn:
  - 0962-8924
publication_status: published
publisher: Cell Press
quality_controlled: '1'
scopus_import: '1'
status: public
title: Rigidity transitions in development and disease
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 32
year: '2022'
...
---
_id: '9794'
abstract:
- lang: eng
  text: 'Lymph nodes (LNs) comprise two main structural elements: fibroblastic reticular
    cells that form dedicated niches for immune cell interaction and capsular fibroblasts
    that build a shell around the organ. Immunological challenge causes LNs to increase
    more than tenfold in size within a few days. Here, we characterized the biomechanics
    of LN swelling on the cellular and organ scale. We identified lymphocyte trapping
    by influx and proliferation as drivers of an outward pressure force, causing fibroblastic
    reticular cells of the T-zone (TRCs) and their associated conduits to stretch.
    After an initial phase of relaxation, TRCs sensed the resulting strain through
    cell matrix adhesions, which coordinated local growth and remodeling of the stromal
    network. While the expanded TRC network readopted its typical configuration, a
    massive fibrotic reaction of the organ capsule set in and countered further organ
    expansion. Thus, different fibroblast populations mechanically control LN swelling
    in a multitier fashion.'
acknowledged_ssus:
- _id: Bio
- _id: EM-Fac
- _id: PreCl
- _id: LifeSc
acknowledgement: This research was supported by the Scientific Service Units of IST
  Austria through resources provided by the Imaging and Optics, Electron Microscopy,
  Preclinical and Life Science Facilities. We thank C. Moussion for providing anti-PNAd
  antibody and D. Critchley for Talin1-floxed mice, and E. Papusheva for providing
  a custom 3D channel alignment script. This work was supported by a European Research
  Council grant ERC-CoG-72437 to M.S. M.H. was supported by Czech Sciencundation GACR
  20-24603Y and Charles University PRIMUS/20/MED/013.
article_processing_charge: No
article_type: original
author:
- first_name: Frank P
  full_name: Assen, Frank P
  id: 3A8E7F24-F248-11E8-B48F-1D18A9856A87
  last_name: Assen
  orcid: 0000-0003-3470-6119
- first_name: Jun
  full_name: Abe, Jun
  last_name: Abe
- first_name: Miroslav
  full_name: Hons, Miroslav
  id: 4167FE56-F248-11E8-B48F-1D18A9856A87
  last_name: Hons
  orcid: 0000-0002-6625-3348
- first_name: Robert
  full_name: Hauschild, Robert
  id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
  last_name: Hauschild
  orcid: 0000-0001-9843-3522
- first_name: Shayan
  full_name: Shamipour, Shayan
  id: 40B34FE2-F248-11E8-B48F-1D18A9856A87
  last_name: Shamipour
- first_name: Walter
  full_name: Kaufmann, Walter
  id: 3F99E422-F248-11E8-B48F-1D18A9856A87
  last_name: Kaufmann
  orcid: 0000-0001-9735-5315
- first_name: Tommaso
  full_name: Costanzo, Tommaso
  id: D93824F4-D9BA-11E9-BB12-F207E6697425
  last_name: Costanzo
  orcid: 0000-0001-9732-3815
- first_name: Gabriel
  full_name: Krens, Gabriel
  id: 2B819732-F248-11E8-B48F-1D18A9856A87
  last_name: Krens
  orcid: 0000-0003-4761-5996
- first_name: Markus
  full_name: Brown, Markus
  id: 3DAB9AFC-F248-11E8-B48F-1D18A9856A87
  last_name: Brown
- first_name: Burkhard
  full_name: Ludewig, Burkhard
  last_name: Ludewig
- first_name: Simon
  full_name: Hippenmeyer, Simon
  id: 37B36620-F248-11E8-B48F-1D18A9856A87
  last_name: Hippenmeyer
  orcid: 0000-0003-2279-1061
- first_name: Carl-Philipp J
  full_name: Heisenberg, Carl-Philipp J
  id: 39427864-F248-11E8-B48F-1D18A9856A87
  last_name: Heisenberg
  orcid: 0000-0002-0912-4566
- first_name: Wolfgang
  full_name: Weninger, Wolfgang
  last_name: Weninger
- first_name: Edouard B
  full_name: Hannezo, Edouard B
  id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
  last_name: Hannezo
  orcid: 0000-0001-6005-1561
- first_name: Sanjiv A.
  full_name: Luther, Sanjiv A.
  last_name: Luther
- first_name: Jens V.
  full_name: Stein, Jens V.
  last_name: Stein
- first_name: Michael K
  full_name: Sixt, Michael K
  id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
  last_name: Sixt
  orcid: 0000-0002-4561-241X
citation:
  ama: Assen FP, Abe J, Hons M, et al. Multitier mechanics control stromal adaptations
    in swelling lymph nodes. <i>Nature Immunology</i>. 2022;23:1246-1255. doi:<a href="https://doi.org/10.1038/s41590-022-01257-4">10.1038/s41590-022-01257-4</a>
  apa: Assen, F. P., Abe, J., Hons, M., Hauschild, R., Shamipour, S., Kaufmann, W.,
    … Sixt, M. K. (2022). Multitier mechanics control stromal adaptations in swelling
    lymph nodes. <i>Nature Immunology</i>. Springer Nature. <a href="https://doi.org/10.1038/s41590-022-01257-4">https://doi.org/10.1038/s41590-022-01257-4</a>
  chicago: Assen, Frank P, Jun Abe, Miroslav Hons, Robert Hauschild, Shayan Shamipour,
    Walter Kaufmann, Tommaso Costanzo, et al. “Multitier Mechanics Control Stromal
    Adaptations in Swelling Lymph Nodes.” <i>Nature Immunology</i>. Springer Nature,
    2022. <a href="https://doi.org/10.1038/s41590-022-01257-4">https://doi.org/10.1038/s41590-022-01257-4</a>.
  ieee: F. P. Assen <i>et al.</i>, “Multitier mechanics control stromal adaptations
    in swelling lymph nodes,” <i>Nature Immunology</i>, vol. 23. Springer Nature,
    pp. 1246–1255, 2022.
  ista: Assen FP, Abe J, Hons M, Hauschild R, Shamipour S, Kaufmann W, Costanzo T,
    Krens G, Brown M, Ludewig B, Hippenmeyer S, Heisenberg C-PJ, Weninger W, Hannezo
    EB, Luther SA, Stein JV, Sixt MK. 2022. Multitier mechanics control stromal adaptations
    in swelling lymph nodes. Nature Immunology. 23, 1246–1255.
  mla: Assen, Frank P., et al. “Multitier Mechanics Control Stromal Adaptations in
    Swelling Lymph Nodes.” <i>Nature Immunology</i>, vol. 23, Springer Nature, 2022,
    pp. 1246–55, doi:<a href="https://doi.org/10.1038/s41590-022-01257-4">10.1038/s41590-022-01257-4</a>.
  short: F.P. Assen, J. Abe, M. Hons, R. Hauschild, S. Shamipour, W. Kaufmann, T.
    Costanzo, G. Krens, M. Brown, B. Ludewig, S. Hippenmeyer, C.-P.J. Heisenberg,
    W. Weninger, E.B. Hannezo, S.A. Luther, J.V. Stein, M.K. Sixt, Nature Immunology
    23 (2022) 1246–1255.
corr_author: '1'
date_created: 2021-08-06T09:09:11Z
date_published: 2022-07-11T00:00:00Z
date_updated: 2025-06-11T13:52:43Z
day: '11'
ddc:
- '570'
department:
- _id: SiHi
- _id: CaHe
- _id: EdHa
- _id: EM-Fac
- _id: Bio
- _id: MiSi
doi: 10.1038/s41590-022-01257-4
ec_funded: 1
external_id:
  isi:
  - '000822975900002'
  pmid:
  - '35817845'
file:
- access_level: open_access
  checksum: 628e7b49809f22c75b428842efe70c68
  content_type: application/pdf
  creator: dernst
  date_created: 2022-07-25T07:11:32Z
  date_updated: 2022-07-25T07:11:32Z
  file_id: '11642'
  file_name: 2022_NatureImmunology_Assen.pdf
  file_size: 11475325
  relation: main_file
  success: 1
file_date_updated: 2022-07-25T07:11:32Z
fulldoi: https://doi.org/10.1038/s41590-022-01257-4
has_accepted_license: '1'
intvolume: '        23'
isi: 1
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
page: 1246-1255
pmid: 1
project:
- _id: 25FE9508-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '724373'
  name: Cellular Navigation Along Spatial Gradients
publication: Nature Immunology
publication_identifier:
  eissn:
  - 1529-2916
  issn:
  - 1529-2908
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Multitier mechanics control stromal adaptations in swelling lymph nodes
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 23
year: '2022'
...
---
_id: '13058'
abstract:
- lang: eng
  text: The zip file includes source data used in the main text of the manuscript
    "Theory of branching morphogenesis by local interactions and global guidance",
    as well as a representative Jupyter notebook to reproduce the main figures. A
    sample script for the simulations of branching and annihilating random walks is
    also included (Sample_script_for_simulations_of_BARWs.ipynb) to generate exemplary
    branched networks under external guidance. A detailed description of the simulation
    setup is provided in the supplementary information of the manuscipt.
article_processing_charge: No
author:
- first_name: Mehmet C
  full_name: Ucar, Mehmet C
  id: 50B2A802-6007-11E9-A42B-EB23E6697425
  last_name: Ucar
  orcid: 0000-0003-0506-4217
citation:
  ama: Ucar MC. Source data for the manuscript “Theory of branching morphogenesis
    by local interactions and global guidance.” 2021. doi:<a href="https://doi.org/10.5281/ZENODO.5257160">10.5281/ZENODO.5257160</a>
  apa: Ucar, M. C. (2021). Source data for the manuscript “Theory of branching morphogenesis
    by local interactions and global guidance.” Zenodo. <a href="https://doi.org/10.5281/ZENODO.5257160">https://doi.org/10.5281/ZENODO.5257160</a>
  chicago: Ucar, Mehmet C. “Source Data for the Manuscript ‘Theory of Branching Morphogenesis
    by Local Interactions and Global Guidance.’” Zenodo, 2021. <a href="https://doi.org/10.5281/ZENODO.5257160">https://doi.org/10.5281/ZENODO.5257160</a>.
  ieee: M. C. Ucar, “Source data for the manuscript ‘Theory of branching morphogenesis
    by local interactions and global guidance.’” Zenodo, 2021.
  ista: Ucar MC. 2021. Source data for the manuscript ‘Theory of branching morphogenesis
    by local interactions and global guidance’, Zenodo, <a href="https://doi.org/10.5281/ZENODO.5257160">10.5281/ZENODO.5257160</a>.
  mla: Ucar, Mehmet C. <i>Source Data for the Manuscript “Theory of Branching Morphogenesis
    by Local Interactions and Global Guidance.”</i> Zenodo, 2021, doi:<a href="https://doi.org/10.5281/ZENODO.5257160">10.5281/ZENODO.5257160</a>.
  short: M.C. Ucar, (2021).
corr_author: '1'
date_created: 2023-05-23T13:46:34Z
date_published: 2021-08-25T00:00:00Z
date_updated: 2025-04-15T06:54:54Z
day: '25'
ddc:
- '570'
department:
- _id: EdHa
doi: 10.5281/ZENODO.5257160
fulldoi: https://doi.org/10.5281/ZENODO.5257160
main_file_link:
- open_access: '1'
  url: https://doi.org/10.5281/zenodo.5257161
month: '08'
oa: 1
oa_version: Published Version
publisher: Zenodo
related_material:
  record:
  - id: '10402'
    relation: used_in_publication
    status: public
status: public
title: Source data for the manuscript "Theory of branching morphogenesis by local
  interactions and global guidance"
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: research_data_reference
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2021'
...
---
_id: '13068'
abstract:
- lang: eng
  text: Source data and source code for the graphs in "Spatiotemporal dynamics of
    self-organized branching pancreatic cancer-derived organoids".
article_processing_charge: No
author:
- first_name: Samuel
  full_name: Randriamanantsoa, Samuel
  last_name: Randriamanantsoa
- first_name: Aristeidis
  full_name: Papargyriou, Aristeidis
  last_name: Papargyriou
- first_name: Carlo
  full_name: Maurer, Carlo
  last_name: Maurer
- first_name: Katja
  full_name: Peschke, Katja
  last_name: Peschke
- first_name: Maximilian
  full_name: Schuster, Maximilian
  last_name: Schuster
- first_name: Giulia
  full_name: Zecchin, Giulia
  last_name: Zecchin
- first_name: Katja
  full_name: Steiger, Katja
  last_name: Steiger
- first_name: Rupert
  full_name: Öllinger, Rupert
  last_name: Öllinger
- first_name: Dieter
  full_name: Saur, Dieter
  last_name: Saur
- first_name: Christina
  full_name: Scheel, Christina
  last_name: Scheel
- first_name: Roland
  full_name: Rad, Roland
  last_name: Rad
- first_name: Edouard B
  full_name: Hannezo, Edouard B
  id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
  last_name: Hannezo
  orcid: 0000-0001-6005-1561
- first_name: Maximilian
  full_name: Reichert, Maximilian
  last_name: Reichert
- first_name: Andreas R.
  full_name: Bausch, Andreas R.
  last_name: Bausch
citation:
  ama: Randriamanantsoa S, Papargyriou A, Maurer C, et al. Spatiotemporal dynamics
    of self-organized branching in pancreas-derived organoids. 2021. doi:<a href="https://doi.org/10.5281/ZENODO.5148117">10.5281/ZENODO.5148117</a>
  apa: Randriamanantsoa, S., Papargyriou, A., Maurer, C., Peschke, K., Schuster, M.,
    Zecchin, G., … Bausch, A. R. (2021). Spatiotemporal dynamics of self-organized
    branching in pancreas-derived organoids. Zenodo. <a href="https://doi.org/10.5281/ZENODO.5148117">https://doi.org/10.5281/ZENODO.5148117</a>
  chicago: Randriamanantsoa, Samuel, Aristeidis Papargyriou, Carlo Maurer, Katja Peschke,
    Maximilian Schuster, Giulia Zecchin, Katja Steiger, et al. “Spatiotemporal Dynamics
    of Self-Organized Branching in Pancreas-Derived Organoids.” Zenodo, 2021. <a href="https://doi.org/10.5281/ZENODO.5148117">https://doi.org/10.5281/ZENODO.5148117</a>.
  ieee: S. Randriamanantsoa <i>et al.</i>, “Spatiotemporal dynamics of self-organized
    branching in pancreas-derived organoids.” Zenodo, 2021.
  ista: Randriamanantsoa S, Papargyriou A, Maurer C, Peschke K, Schuster M, Zecchin
    G, Steiger K, Öllinger R, Saur D, Scheel C, Rad R, Hannezo EB, Reichert M, Bausch
    AR. 2021. Spatiotemporal dynamics of self-organized branching in pancreas-derived
    organoids, Zenodo, <a href="https://doi.org/10.5281/ZENODO.5148117">10.5281/ZENODO.5148117</a>.
  mla: Randriamanantsoa, Samuel, et al. <i>Spatiotemporal Dynamics of Self-Organized
    Branching in Pancreas-Derived Organoids</i>. Zenodo, 2021, doi:<a href="https://doi.org/10.5281/ZENODO.5148117">10.5281/ZENODO.5148117</a>.
  short: S. Randriamanantsoa, A. Papargyriou, C. Maurer, K. Peschke, M. Schuster,
    G. Zecchin, K. Steiger, R. Öllinger, D. Saur, C. Scheel, R. Rad, E.B. Hannezo,
    M. Reichert, A.R. Bausch, (2021).
date_created: 2023-05-23T16:39:24Z
date_published: 2021-07-30T00:00:00Z
date_updated: 2025-06-11T13:53:54Z
day: '30'
ddc:
- '570'
department:
- _id: EdHa
doi: 10.5281/ZENODO.5148117
fulldoi: https://doi.org/10.5281/ZENODO.5148117
main_file_link:
- open_access: '1'
  url: https://doi.org/10.5281/zenodo.6577226
month: '07'
oa: 1
oa_version: Published Version
publisher: Zenodo
related_material:
  record:
  - id: '12217'
    relation: used_in_publication
    status: public
status: public
title: Spatiotemporal dynamics of self-organized branching in pancreas-derived organoids
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
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  short: CC BY (4.0)
type: research_data_reference
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2021'
...
---
_id: '10178'
abstract:
- lang: eng
  text: In dense biological tissues, cell types performing different roles remain
    segregated by maintaining sharp interfaces. To better understand the mechanisms
    for such sharp compartmentalization, we study the effect of an imposed heterotypic
    tension at the interface between two distinct cell types in a fully 3D Voronoi
    model for confluent tissues. We find that cells rapidly sort and self-organize
    to generate a tissue-scale interface between cell types, and cells adjacent to
    this interface exhibit signature geometric features including nematic-like ordering,
    bimodal facet areas, and registration, or alignment, of cell centers on either
    side of the two-tissue interface. The magnitude of these features scales directly
    with the magnitude of the imposed tension, suggesting that biologists can estimate
    the magnitude of tissue surface tension between two tissue types simply by segmenting
    a 3D tissue. To uncover the underlying physical mechanisms driving these geometric
    features, we develop two minimal, ordered models using two different underlying
    lattices that identify an energetic competition between bulk cell shapes and tissue
    interface area. When the interface area dominates, changes to neighbor topology
    are costly and occur less frequently, which generates the observed geometric features.
acknowledgement: "We thank Paula Sanematsu, Matthias Merkel, Daniel Sussman, Cristina
  Marchetti and Edouard Hannezo for helpful discussions, and M Merkel for developing
  and sharing the original version of the 3D Voronoi code. This work was primarily
  funded by NSF-PHY-1607416, NSF-PHY-2014192 , and are in the division of physics
  at the National Science Foundation. PS and MLM acknowledge additional support from
  Simons Grant No. 454947.\r\n"
article_number: '093043'
article_processing_charge: Yes
article_type: original
arxiv: 1
author:
- first_name: Preeti
  full_name: Sahu, Preeti
  id: 55BA52EE-A185-11EA-88FD-18AD3DDC885E
  last_name: Sahu
- first_name: J. M.
  full_name: Schwarz, J. M.
  last_name: Schwarz
- first_name: M. Lisa
  full_name: Manning, M. Lisa
  last_name: Manning
citation:
  ama: Sahu P, Schwarz JM, Manning ML. Geometric signatures of tissue surface tension
    in a three-dimensional model of confluent tissue. <i>New Journal of Physics</i>.
    2021;23(9). doi:<a href="https://doi.org/10.1088/1367-2630/ac23f1">10.1088/1367-2630/ac23f1</a>
  apa: Sahu, P., Schwarz, J. M., &#38; Manning, M. L. (2021). Geometric signatures
    of tissue surface tension in a three-dimensional model of confluent tissue. <i>New
    Journal of Physics</i>. IOP Publishing. <a href="https://doi.org/10.1088/1367-2630/ac23f1">https://doi.org/10.1088/1367-2630/ac23f1</a>
  chicago: Sahu, Preeti, J. M. Schwarz, and M. Lisa Manning. “Geometric Signatures
    of Tissue Surface Tension in a Three-Dimensional Model of Confluent Tissue.” <i>New
    Journal of Physics</i>. IOP Publishing, 2021. <a href="https://doi.org/10.1088/1367-2630/ac23f1">https://doi.org/10.1088/1367-2630/ac23f1</a>.
  ieee: P. Sahu, J. M. Schwarz, and M. L. Manning, “Geometric signatures of tissue
    surface tension in a three-dimensional model of confluent tissue,” <i>New Journal
    of Physics</i>, vol. 23, no. 9. IOP Publishing, 2021.
  ista: Sahu P, Schwarz JM, Manning ML. 2021. Geometric signatures of tissue surface
    tension in a three-dimensional model of confluent tissue. New Journal of Physics.
    23(9), 093043.
  mla: Sahu, Preeti, et al. “Geometric Signatures of Tissue Surface Tension in a Three-Dimensional
    Model of Confluent Tissue.” <i>New Journal of Physics</i>, vol. 23, no. 9, 093043,
    IOP Publishing, 2021, doi:<a href="https://doi.org/10.1088/1367-2630/ac23f1">10.1088/1367-2630/ac23f1</a>.
  short: P. Sahu, J.M. Schwarz, M.L. Manning, New Journal of Physics 23 (2021).
date_created: 2021-10-24T22:01:34Z
date_published: 2021-09-29T00:00:00Z
date_updated: 2026-04-02T13:54:56Z
day: '29'
ddc:
- '570'
department:
- _id: EdHa
doi: 10.1088/1367-2630/ac23f1
external_id:
  arxiv:
  - '2102.05397'
  isi:
  - '000702042400001'
file:
- access_level: open_access
  checksum: ace603e8f0962b3ba55f23fa34f57764
  content_type: application/pdf
  creator: cziletti
  date_created: 2021-10-28T12:06:01Z
  date_updated: 2021-10-28T12:06:01Z
  file_id: '10193'
  file_name: 2021_NewJPhys_Sahu.pdf
  file_size: 2215016
  relation: main_file
  success: 1
file_date_updated: 2021-10-28T12:06:01Z
fulldoi: https://doi.org/10.1088/1367-2630/ac23f1
has_accepted_license: '1'
intvolume: '        23'
isi: 1
issue: '9'
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
publication: New Journal of Physics
publication_identifier:
  eissn:
  - 1367-2630
publication_status: published
publisher: IOP Publishing
quality_controlled: '1'
scopus_import: '1'
status: public
title: Geometric signatures of tissue surface tension in a three-dimensional model
  of confluent tissue
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
volume: 23
year: '2021'
...
