---
_id: '17191'
abstract:
- lang: eng
text: Dendritic cells migrate to and from lymph nodes in response to chemokine gradients.Data
now show that steady-state migration of these cells can be triggered by a mechanosensitive
pathway.
article_processing_charge: No
article_type: letter_note
author:
- first_name: Sergio
full_name: Lembo, Sergio
id: d993a7b2-292f-11ed-aaac-fb045a912e31
last_name: Lembo
orcid: 0000-0002-2253-8771
- 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: Lembo S, Sixt MK. Nuclear squeezing wakes up dendritic cells. Nature Immunology.
2024;25:1131–1132. doi:10.1038/s41590-024-01881-2
apa: Lembo, S., & Sixt, M. K. (2024). Nuclear squeezing wakes up dendritic cells.
Nature Immunology. Springer Nature. https://doi.org/10.1038/s41590-024-01881-2
chicago: Lembo, Sergio, and Michael K Sixt. “Nuclear Squeezing Wakes up Dendritic
Cells.” Nature Immunology. Springer Nature, 2024. https://doi.org/10.1038/s41590-024-01881-2.
ieee: S. Lembo and M. K. Sixt, “Nuclear squeezing wakes up dendritic cells,” Nature
Immunology, vol. 25. Springer Nature, pp. 1131–1132, 2024.
ista: Lembo S, Sixt MK. 2024. Nuclear squeezing wakes up dendritic cells. Nature
Immunology. 25, 1131–1132.
mla: Lembo, Sergio, and Michael K. Sixt. “Nuclear Squeezing Wakes up Dendritic Cells.”
Nature Immunology, vol. 25, Springer Nature, 2024, pp. 1131–1132, doi:10.1038/s41590-024-01881-2.
short: S. Lembo, M.K. Sixt, Nature Immunology 25 (2024) 1131–1132.
corr_author: '1'
date_created: 2024-06-30T22:01:05Z
date_published: 2024-06-21T00:00:00Z
date_updated: 2025-09-08T08:06:56Z
day: '21'
department:
- _id: MiSi
doi: 10.1038/s41590-024-01881-2
external_id:
isi:
- '001251509300001'
pmid:
- '38907047'
intvolume: ' 25'
isi: 1
language:
- iso: eng
month: '06'
oa_version: None
page: '1131–1132 '
pmid: 1
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: Nuclear squeezing wakes up dendritic cells
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 25
year: '2024'
...
---
_id: '17233'
abstract:
- lang: eng
text: CRISPR-Cas9 technology has become an essential tool for plant genome editing.
Recent advancements have significantly improved the ability to target multiple
genes simultaneously within the same genetic background through various strategies.
Additionally, there has been significant progress in developing methods for inducible
or tissue-specific editing. These advancements offer numerous possibilities for
tailored genome modifications. Building upon existing research, we have developed
an optimized and modular strategy allowing the targeting of several genes simultaneously
in combination with the synchronized expression of the Cas9 endonuclease in the
egg cell. This system allows significant editing efficiency while avoiding mosaicism.
In addition, the versatile system we propose allows adaptation to inducible and/or
tissue-specific edition according to the promoter chosen to drive the expression
of the Cas9 gene. Here, we describe a step-by-step protocol for generating the
binary vector necessary for establishing Arabidopsis edited lines using a versatile
cloning strategy that combines Gateway® and Golden Gate technologies. We describe
a versatile system that allows the cloning of as many guides as needed to target
DNA, which can be multiplexed into a polycistronic gene and combined in the same
construct with sequences for the expression of the Cas9 endonuclease. The expression
of Cas9 is controlled by selecting from among a collection of promoters, including
constitutive, inducible, ubiquitous, or tissue-specific promoters. Only one vector
containing the polycistronic gene (tRNA-sgRNA) needs to be constructed. For that,
sgRNA (composed of protospacers chosen to target the gene of interest and sgRNA
scaffold) is cloned in tandem with the pre-tRNA sequence. Then, a single recombination
reaction is required to assemble the promoter, the zCas9 coding sequence, and
the tRNA-gRNA polycistronic gene. Each element is cloned in an entry vector and
finally assembled according to the Multisite Gateway® Technology. Here, we detail
the process to express zCas9 under the control of egg cell promoter fused to enhancer
sequence (EC1.2en-EC1.1p) and to simultaneously target two multiple C2 domains
and transmembrane region protein genes (MCTP3 and MCTP4, respectively at3g57880
and at1g51570), using one or two sgRNA per gene.
acknowledgement: This work was supported by the European Research Council (ERC) under
the European Union’s Horizon 2020 research and innovation program (project 772103-BRIDGING
to E.M.B.).
article_number: e5029
article_processing_charge: Yes
article_type: original
author:
- first_name: Ziqiang
full_name: Li, Ziqiang
id: 922e68bb-1727-11ee-857c-966e8cc1b6c3
last_name: Li
- first_name: Jennifer
full_name: Huard, Jennifer
last_name: Huard
- first_name: Emmanuelle M.
full_name: Bayer, Emmanuelle M.
last_name: Bayer
- first_name: Valérie
full_name: Wattelet-Boyer, Valérie
last_name: Wattelet-Boyer
citation:
ama: LI Z, Huard J, Bayer EM, Wattelet-Boyer V. Versatile cloning strategy for efficient
multigene editing in Arabidopsis. Bio-protocol. 2024;14(13). doi:10.21769/BioProtoc.5029
apa: LI, Z., Huard, J., Bayer, E. M., & Wattelet-Boyer, V. (2024). Versatile
cloning strategy for efficient multigene editing in Arabidopsis. Bio-Protocol.
Bio-Protocol. https://doi.org/10.21769/BioProtoc.5029
chicago: LI, ZIQIANG, Jennifer Huard, Emmanuelle M. Bayer, and Valérie Wattelet-Boyer.
“Versatile Cloning Strategy for Efficient Multigene Editing in Arabidopsis.” Bio-Protocol.
Bio-Protocol, 2024. https://doi.org/10.21769/BioProtoc.5029.
ieee: Z. LI, J. Huard, E. M. Bayer, and V. Wattelet-Boyer, “Versatile cloning strategy
for efficient multigene editing in Arabidopsis,” Bio-protocol, vol. 14,
no. 13. Bio-Protocol, 2024.
ista: LI Z, Huard J, Bayer EM, Wattelet-Boyer V. 2024. Versatile cloning strategy
for efficient multigene editing in Arabidopsis. Bio-protocol. 14(13), e5029.
mla: LI, ZIQIANG, et al. “Versatile Cloning Strategy for Efficient Multigene Editing
in Arabidopsis.” Bio-Protocol, vol. 14, no. 13, e5029, Bio-Protocol, 2024,
doi:10.21769/BioProtoc.5029.
short: Z. LI, J. Huard, E.M. Bayer, V. Wattelet-Boyer, Bio-Protocol 14 (2024).
date_created: 2024-07-14T22:01:11Z
date_published: 2024-07-05T00:00:00Z
date_updated: 2025-03-06T10:28:18Z
day: '05'
ddc:
- '570'
department:
- _id: MiSi
doi: 10.21769/BioProtoc.5029
external_id:
pmid:
- '39007160'
file:
- access_level: open_access
checksum: c8671c0ad483da6407cb16cc3fef1990
content_type: application/pdf
creator: dernst
date_created: 2024-07-16T06:16:11Z
date_updated: 2024-07-16T06:16:11Z
file_id: '17242'
file_name: 2024_BioProtocol_Li.pdf
file_size: 2896048
relation: main_file
success: 1
file_date_updated: 2024-07-16T06:16:11Z
has_accepted_license: '1'
intvolume: ' 14'
issue: '13'
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
pmid: 1
publication: Bio-protocol
publication_identifier:
eissn:
- 2331-8325
publication_status: published
publisher: Bio-Protocol
quality_controlled: '1'
scopus_import: '1'
status: public
title: Versatile cloning strategy for efficient multigene editing in Arabidopsis
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: '2024'
...
---
_id: '17279'
abstract:
- lang: eng
text: In a recent issue of Cell, Zhang et al.1 demonstrate that mechanical features
of a solid tumor can drive T cells into dysfunctionality and identify pathways
that revert this “exhausted” state.
article_processing_charge: No
article_type: review
author:
- first_name: Mario
full_name: Avellaneda Sarrió, Mario
id: DC4BA84C-56E6-11EA-AD5D-348C3DDC885E
last_name: Avellaneda Sarrió
orcid: 0000-0001-6406-524X
- 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: Avellaneda Sarrió M, Sixt MK. Rescuing T cells from stiff tumors. Cell Chemical
Biology. 2024;31(7):1242-1243. doi:10.1016/j.chembiol.2024.06.011
apa: Avellaneda Sarrió, M., & Sixt, M. K. (2024). Rescuing T cells from stiff
tumors. Cell Chemical Biology. Elsevier. https://doi.org/10.1016/j.chembiol.2024.06.011
chicago: Avellaneda Sarrió, Mario, and Michael K Sixt. “Rescuing T Cells from Stiff
Tumors.” Cell Chemical Biology. Elsevier, 2024. https://doi.org/10.1016/j.chembiol.2024.06.011.
ieee: M. Avellaneda Sarrió and M. K. Sixt, “Rescuing T cells from stiff tumors,”
Cell Chemical Biology, vol. 31, no. 7. Elsevier, pp. 1242–1243, 2024.
ista: Avellaneda Sarrió M, Sixt MK. 2024. Rescuing T cells from stiff tumors. Cell
Chemical Biology. 31(7), 1242–1243.
mla: Avellaneda Sarrió, Mario, and Michael K. Sixt. “Rescuing T Cells from Stiff
Tumors.” Cell Chemical Biology, vol. 31, no. 7, Elsevier, 2024, pp. 1242–43,
doi:10.1016/j.chembiol.2024.06.011.
short: M. Avellaneda Sarrió, M.K. Sixt, Cell Chemical Biology 31 (2024) 1242–1243.
corr_author: '1'
date_created: 2024-07-21T22:01:00Z
date_published: 2024-07-18T00:00:00Z
date_updated: 2025-09-08T08:27:03Z
day: '18'
department:
- _id: MiSi
doi: 10.1016/j.chembiol.2024.06.011
external_id:
isi:
- '001275725000001'
pmid:
- '39029454'
intvolume: ' 31'
isi: 1
issue: '7'
language:
- iso: eng
month: '07'
oa_version: None
page: 1242-1243
pmid: 1
publication: Cell Chemical Biology
publication_identifier:
eissn:
- 2451-9448
issn:
- 2451-9456
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Rescuing T cells from stiff tumors
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 31
year: '2024'
...
---
_id: '17284'
abstract:
- lang: eng
text: Platelet homeostasis is essential for vascular integrity and immune defence1,2.
Although the process of platelet formation by fragmenting megakaryocytes (MKs;
thrombopoiesis) has been extensively studied, the cellular and molecular mechanisms
required to constantly replenish the pool of MKs by their progenitor cells (megakaryopoiesis)
remains unclear3,4. Here we use intravital imaging to track the cellular dynamics
of megakaryopoiesis over days. We identify plasmacytoid dendritic cells (pDCs)
as homeostatic sensors that monitor the bone marrow for apoptotic MKs and deliver
IFNα to the MK niche triggering local on-demand proliferation and maturation of
MK progenitors. This pDC-dependent feedback loop is crucial for MK and platelet
homeostasis at steady state and under stress. pDCs are best known for their ability
to function as vigilant detectors of viral infection5. We show that virus-induced
activation of pDCs interferes with their function as homeostatic sensors of megakaryopoiesis.
Consequently, activation of pDCs by SARS-CoV-2 leads to excessive megakaryopoiesis.
Together, we identify a pDC-dependent homeostatic circuit that involves innate
immune sensing and demand-adapted release of inflammatory mediators to maintain
homeostasis of the megakaryocytic lineage.
acknowledgement: 'We thank S. Helmer, N. Blount, E. Raatz and Z. Sisic for technical
assistance. This work was funded by the Deutsche Forschungsgemeinschaft (DFG, German
Research Foundation) SFB 1123 (S.M. project B06); SFB 914 (S.M. projects B02 and
Z01, H.I.-A. project Z01, S.S. project A06, K.S. project B02, C. Schulz project
A10, B.W. project A02, C. Scheiermann project B09); SFB 1054 (T.B. project B03);
FOR2033 (F.G., R.A.J.O., S.M.); Individual research grant project ID: 514478744
(F.G.); Heisenberg Programme project ID: 514477451 (F.G.); the DZHK (German Center
for Cardiovascular Research) (MHA 1.4VD (S.M.), Postdoc Start-up Grant, 81×3600213
(F.G.)); and LMUexcellence NFF (F.G.). W.F. received funding from China Scholarship
Council (CSC, no. 201306270012). P.B. is supported by the German Research Foundation
(DFG, project IDs 322900939, 432698239 and 445703531), European Research Council
(ERC Consolidator grant no. 101001791) and the Federal Ministry of Education and
Research (BMBF, STOP-FSGS-01GM2202C and NATON within the framework of the Network
of University Medicine, no. 01KX2121). S.v.S. is supported by the START-Program
of the Faculty of Medicine of the RWTH Aachen University (AZ 125/17). A.D. and S.E.
are supported by the German Research Foundation (SFB TRR 267); S.E. by the BMBF
in the framework of the Cluster4future program (CNATM—Cluster for Nucleic Acid Therapeutics
Munich). This project has received funding from the European Research Council (ERC)
under the European Union’s Horizon 2020 research and innovation programme (grant
agreement no. 833440 to S.M.). F.G. received funding from the European Union’s Horizon
2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement
no. 747687. The project is funded by the European Union (ERC, MEKanics, 101078110).
Views and opinions expressed are those of the author(s) only and do not necessarily
reflect those of the European Union or the European Research Council Executive Agency.
Neither the European Union nor the granting authority can be held responsible for
them.'
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Florian R
full_name: Gärtner, Florian R
id: 397A88EE-F248-11E8-B48F-1D18A9856A87
last_name: Gärtner
orcid: 0000-0001-6120-3723
- first_name: Hellen
full_name: Ishikawa-Ankerhold, Hellen
last_name: Ishikawa-Ankerhold
- first_name: Susanne
full_name: Stutte, Susanne
last_name: Stutte
- first_name: Wenwen
full_name: Fu, Wenwen
last_name: Fu
- first_name: Jutta
full_name: Weitz, Jutta
last_name: Weitz
- first_name: Anne
full_name: Dueck, Anne
last_name: Dueck
- first_name: Bhavishya
full_name: Nelakuditi, Bhavishya
last_name: Nelakuditi
- first_name: Valeria
full_name: Fumagalli, Valeria
last_name: Fumagalli
- first_name: Dominic
full_name: Van Den Heuvel, Dominic
last_name: Van Den Heuvel
- first_name: Larissa
full_name: Belz, Larissa
last_name: Belz
- first_name: Gulnoza
full_name: Sobirova, Gulnoza
last_name: Sobirova
- first_name: Zhe
full_name: Zhang, Zhe
last_name: Zhang
- first_name: Anna
full_name: Titova, Anna
last_name: Titova
- first_name: Alejandro Martinez
full_name: Navarro, Alejandro Martinez
last_name: Navarro
- first_name: Kami
full_name: Pekayvaz, Kami
last_name: Pekayvaz
- first_name: Michael
full_name: Lorenz, Michael
last_name: Lorenz
- first_name: Louisa
full_name: Von Baumgarten, Louisa
last_name: Von Baumgarten
- first_name: Jan
full_name: Kranich, Jan
last_name: Kranich
- first_name: Tobias
full_name: Straub, Tobias
last_name: Straub
- first_name: Bastian
full_name: Popper, Bastian
last_name: Popper
- first_name: Vanessa
full_name: Zheden, Vanessa
id: 39C5A68A-F248-11E8-B48F-1D18A9856A87
last_name: Zheden
orcid: 0000-0002-9438-4783
- first_name: Walter
full_name: Kaufmann, Walter
id: 3F99E422-F248-11E8-B48F-1D18A9856A87
last_name: Kaufmann
orcid: 0000-0001-9735-5315
- first_name: Chenglong
full_name: Guo, Chenglong
last_name: Guo
- first_name: Guido
full_name: Piontek, Guido
last_name: Piontek
- first_name: Saskia
full_name: Von Stillfried, Saskia
last_name: Von Stillfried
- first_name: Peter
full_name: Boor, Peter
last_name: Boor
- first_name: Marco
full_name: Colonna, Marco
last_name: Colonna
- first_name: Sebastian
full_name: Clauß, Sebastian
last_name: Clauß
- first_name: Christian
full_name: Schulz, Christian
last_name: Schulz
- first_name: Thomas
full_name: Brocker, Thomas
last_name: Brocker
- first_name: Barbara
full_name: Walzog, Barbara
last_name: Walzog
- first_name: Christoph
full_name: Scheiermann, Christoph
last_name: Scheiermann
- first_name: William C.
full_name: Aird, William C.
last_name: Aird
- first_name: Claus
full_name: Nerlov, Claus
last_name: Nerlov
- first_name: Konstantin
full_name: Stark, Konstantin
last_name: Stark
- first_name: Tobias
full_name: Petzold, Tobias
last_name: Petzold
- first_name: Stefan
full_name: Engelhardt, Stefan
last_name: Engelhardt
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
- first_name: Robert
full_name: Hauschild, Robert
id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
last_name: Hauschild
orcid: 0000-0001-9843-3522
- first_name: Martina
full_name: Rudelius, Martina
last_name: Rudelius
- first_name: Robert A.J.
full_name: Oostendorp, Robert A.J.
last_name: Oostendorp
- first_name: Matteo
full_name: Iannacone, Matteo
last_name: Iannacone
- first_name: Matthias
full_name: Heinig, Matthias
last_name: Heinig
- first_name: Steffen
full_name: Massberg, Steffen
last_name: Massberg
citation:
ama: Gärtner FR, Ishikawa-Ankerhold H, Stutte S, et al. Plasmacytoid dendritic cells
control homeostasis of megakaryopoiesis. Nature. 2024;631:645-653. doi:10.1038/s41586-024-07671-y
apa: Gärtner, F. R., Ishikawa-Ankerhold, H., Stutte, S., Fu, W., Weitz, J., Dueck,
A., … Massberg, S. (2024). Plasmacytoid dendritic cells control homeostasis of
megakaryopoiesis. Nature. Springer Nature. https://doi.org/10.1038/s41586-024-07671-y
chicago: Gärtner, Florian R, Hellen Ishikawa-Ankerhold, Susanne Stutte, Wenwen Fu,
Jutta Weitz, Anne Dueck, Bhavishya Nelakuditi, et al. “Plasmacytoid Dendritic
Cells Control Homeostasis of Megakaryopoiesis.” Nature. Springer Nature,
2024. https://doi.org/10.1038/s41586-024-07671-y.
ieee: F. R. Gärtner et al., “Plasmacytoid dendritic cells control homeostasis
of megakaryopoiesis,” Nature, vol. 631. Springer Nature, pp. 645–653, 2024.
ista: Gärtner FR, Ishikawa-Ankerhold H, Stutte S, Fu W, Weitz J, Dueck A, Nelakuditi
B, Fumagalli V, Van Den Heuvel D, Belz L, Sobirova G, Zhang Z, Titova A, Navarro
AM, Pekayvaz K, Lorenz M, Von Baumgarten L, Kranich J, Straub T, Popper B, Zheden
V, Kaufmann W, Guo C, Piontek G, Von Stillfried S, Boor P, Colonna M, Clauß S,
Schulz C, Brocker T, Walzog B, Scheiermann C, Aird WC, Nerlov C, Stark K, Petzold
T, Engelhardt S, Sixt MK, Hauschild R, Rudelius M, Oostendorp RAJ, Iannacone M,
Heinig M, Massberg S. 2024. Plasmacytoid dendritic cells control homeostasis of
megakaryopoiesis. Nature. 631, 645–653.
mla: Gärtner, Florian R., et al. “Plasmacytoid Dendritic Cells Control Homeostasis
of Megakaryopoiesis.” Nature, vol. 631, Springer Nature, 2024, pp. 645–53,
doi:10.1038/s41586-024-07671-y.
short: F.R. Gärtner, H. Ishikawa-Ankerhold, S. Stutte, W. Fu, J. Weitz, A. Dueck,
B. Nelakuditi, V. Fumagalli, D. Van Den Heuvel, L. Belz, G. Sobirova, Z. Zhang,
A. Titova, A.M. Navarro, K. Pekayvaz, M. Lorenz, L. Von Baumgarten, J. Kranich,
T. Straub, B. Popper, V. Zheden, W. Kaufmann, C. Guo, G. Piontek, S. Von Stillfried,
P. Boor, M. Colonna, S. Clauß, C. Schulz, T. Brocker, B. Walzog, C. Scheiermann,
W.C. Aird, C. Nerlov, K. Stark, T. Petzold, S. Engelhardt, M.K. Sixt, R. Hauschild,
M. Rudelius, R.A.J. Oostendorp, M. Iannacone, M. Heinig, S. Massberg, Nature 631
(2024) 645–653.
corr_author: '1'
date_created: 2024-07-21T22:01:02Z
date_published: 2024-07-18T00:00:00Z
date_updated: 2025-09-08T08:14:25Z
day: '18'
ddc:
- '570'
department:
- _id: EM-Fac
- _id: MiSi
- _id: Bio
doi: 10.1038/s41586-024-07671-y
ec_funded: 1
external_id:
isi:
- '001281636500020'
pmid:
- '38987596'
file:
- access_level: open_access
checksum: aa004afc72d2489f0fb0fcbc9919fbbd
content_type: application/pdf
creator: dernst
date_created: 2024-07-22T06:16:11Z
date_updated: 2024-07-22T06:16:11Z
file_id: '17286'
file_name: 2024_Nature_Gaertner.pdf
file_size: 15704819
relation: main_file
success: 1
file_date_updated: 2024-07-22T06:16:11Z
has_accepted_license: '1'
intvolume: ' 631'
isi: 1
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
page: 645-653
pmid: 1
project:
- _id: 260AA4E2-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '747687'
name: Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells
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/heiniglab/gaertner_megakaryocytes
scopus_import: '1'
status: public
title: Plasmacytoid dendritic cells control homeostasis of megakaryopoiesis
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: 631
year: '2024'
...
---
_id: '18109'
abstract:
- lang: eng
text: Venous thromboembolism (VTE) is a common, deadly disease with an increasing
incidence despite preventive efforts. Clinical observations have associated elevated
antibody concentrations or antibody-based therapies with thrombotic events. However,
how antibodies contribute to thrombosis is unknown. Here, we show that reduced
blood flow enabled immunoglobulin M (IgM) to bind to FcμR and the polymeric immunoglobulin
receptor (pIgR), initiating endothelial activation and platelet recruitment. Subsequently,
the procoagulant surface of activated platelets accommodated antigen- and FcγR-independent
IgG deposition. This leads to classical complement activation, setting in motion
a prothrombotic vicious circle. Key elements of this mechanism were present in
humans in the setting of venous stasis as well as in the dysregulated immunothrombosis
of COVID-19. This antibody-driven thrombosis can be prevented by pharmacologically
targeting complement. Hence, our results uncover antibodies as previously unrecognized
central regulators of thrombosis. These findings carry relevance for therapeutic
application of antibodies and open innovative avenues to target thrombosis without
compromising hemostasis.
acknowledgement: "We thank Michael Carroll (Harvard Medical School, Boston) for providing
Ighmtm1Che, C4−/−, and C3−/− mice; Mark Suter (University of Zurich, Zurich) for
providing Aicda−/− mice; Marina Botto (Imperial College London, London) for providing
C1q−/− and fB−/− mice; Craig Gerard (Harvard Medical School, Boston) for providing
C3aR−/− mice; Falk Nimmerjahn (University Erlangen-Nuernberg, Erlangen) for providing
Fcgr−/−Fcgr2b−/− mice; Karl Lang (University of Duisburg-Essen, Essen) for providing
Fcmr−/− mice; Hans Hengartner and Rolf Zinkernagel (ETH Zurich, Zurich) for providing
KL25 mice; Mark Zabel (University Hospital of Zurich, Zurich) for providing CR2−/−
mice; Christie Ballantyne (Baylor College of Medicine, Houston) for providing CD11c−/−
mice; and Siamon Gordon (University of Oxford, Oxford) for providing CD11b−/− mice.
A.V. wishes to thank Michael Grünaug and dedicates this work to Annette, Rita, and
Hans.\r\nThis project has received funding from the European Research Council (ERC)
under the European Union’s Horizon 2020 research and innovation programme (grant
agreement no. \r\n947611) (K.S.). This study was supported by the Deutsche Forschungsgemeinschaft
through the collaborative research center 914 project B02 (K.S. and S.M.), project
B04 (A.V.), project A01 (M.M.), project B01 (M.S.), the collaborative research center
1123 project B07 (K.S. and S.M.), the collaborative research center 359 (project
A03 [K.S.] and B02 [M.S.]), the international research training group 1911 project
B09 (A.V.), the clinical research unit 303 project 7 (A.V.), cluster of excellence
2167 (A.V.), collaborative research center 1526 project 05 (A.V.), the ANR-DFG project
JAKPOT (K.S.), LMUexcellent (K.S.), and the Deutsche Zentrum für Herz-Kreislauf-Forschung
(PostDoc Grant and partner site project [K.S. and S.M.]). M.I. is supported by the
European Research Council (ERC) Advanced Grant 101141363, ERC Proof of Concept Grant
101138728, Italian Association for Cancer Research (AIRC) Grants 19891 and \r\n22737,
Italian Ministry for University and Research Grants PE00000007 (INF-ACT) and PRIN
\r\n2022FMESXL, Funded Research Agreement from Asher Biotherapeutics, VIR Biotechnology,
and BlueJay Therapeutics. V.F. is supported by the Italian Ministry for University
and Research Grants PE00000007 (INF-ACT) and Fondazione Prossimo Mio."
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Konstantin
full_name: Stark, Konstantin
last_name: Stark
- first_name: Badr
full_name: Kilani, Badr
last_name: Kilani
- first_name: Sven
full_name: Stockhausen, Sven
last_name: Stockhausen
- first_name: Johanna
full_name: Busse, Johanna
last_name: Busse
- first_name: Irene
full_name: Schubert, Irene
last_name: Schubert
- first_name: Thuy Duong
full_name: Tran, Thuy Duong
last_name: Tran
- first_name: Florian R
full_name: Gärtner, Florian R
id: 397A88EE-F248-11E8-B48F-1D18A9856A87
last_name: Gärtner
orcid: 0000-0001-6120-3723
- first_name: Alexander
full_name: Leunig, Alexander
last_name: Leunig
- first_name: Kami
full_name: Pekayvaz, Kami
last_name: Pekayvaz
- first_name: Leo
full_name: Nicolai, Leo
last_name: Nicolai
- first_name: Valeria
full_name: Fumagalli, Valeria
last_name: Fumagalli
- first_name: Julia
full_name: Stermann, Julia
last_name: Stermann
- first_name: Felix
full_name: Stephan, Felix
last_name: Stephan
- first_name: Christian
full_name: David, Christian
last_name: David
- first_name: Martin B.
full_name: Müller, Martin B.
last_name: Müller
- first_name: Birgitta
full_name: Heyman, Birgitta
last_name: Heyman
- first_name: Anja
full_name: Lux, Anja
last_name: Lux
- first_name: Alexandra
full_name: Da Palma Guerreiro, Alexandra
last_name: Da Palma Guerreiro
- first_name: Lukas P.
full_name: Frenzel, Lukas P.
last_name: Frenzel
- first_name: Christoph Q.
full_name: Schmidt, Christoph Q.
last_name: Schmidt
- first_name: Arthur
full_name: Dopler, Arthur
last_name: Dopler
- first_name: Markus
full_name: Moser, Markus
last_name: Moser
- first_name: Sue
full_name: Chandraratne, Sue
last_name: Chandraratne
- first_name: Marie Luise
full_name: Von Brühl, Marie Luise
last_name: Von Brühl
- first_name: Michael
full_name: Lorenz, Michael
last_name: Lorenz
- first_name: Thomas
full_name: Korff, Thomas
last_name: Korff
- first_name: Martina
full_name: Rudelius, Martina
last_name: Rudelius
- first_name: Oliver
full_name: Popp, Oliver
last_name: Popp
- first_name: Marieluise
full_name: Kirchner, Marieluise
last_name: Kirchner
- first_name: Philipp
full_name: Mertins, Philipp
last_name: Mertins
- first_name: Falk
full_name: Nimmerjahn, Falk
last_name: Nimmerjahn
- first_name: Matteo
full_name: Iannacone, Matteo
last_name: Iannacone
- first_name: Markus
full_name: Sperandio, Markus
last_name: Sperandio
- first_name: Bernd
full_name: Engelmann, Bernd
last_name: Engelmann
- first_name: Admar
full_name: Verschoor, Admar
last_name: Verschoor
- first_name: Steffen
full_name: Massberg, Steffen
last_name: Massberg
citation:
ama: Stark K, Kilani B, Stockhausen S, et al. Antibodies and complement are key
drivers of thrombosis. Immunity. 2024;57(9):2140-2156. doi:10.1016/j.immuni.2024.08.007
apa: Stark, K., Kilani, B., Stockhausen, S., Busse, J., Schubert, I., Tran, T. D.,
… Massberg, S. (2024). Antibodies and complement are key drivers of thrombosis.
Immunity. Elsevier. https://doi.org/10.1016/j.immuni.2024.08.007
chicago: Stark, Konstantin, Badr Kilani, Sven Stockhausen, Johanna Busse, Irene
Schubert, Thuy Duong Tran, Florian R Gärtner, et al. “Antibodies and Complement
Are Key Drivers of Thrombosis.” Immunity. Elsevier, 2024. https://doi.org/10.1016/j.immuni.2024.08.007.
ieee: K. Stark et al., “Antibodies and complement are key drivers of thrombosis,”
Immunity, vol. 57, no. 9. Elsevier, pp. 2140–2156, 2024.
ista: Stark K, Kilani B, Stockhausen S, Busse J, Schubert I, Tran TD, Gärtner FR,
Leunig A, Pekayvaz K, Nicolai L, Fumagalli V, Stermann J, Stephan F, David C,
Müller MB, Heyman B, Lux A, Da Palma Guerreiro A, Frenzel LP, Schmidt CQ, Dopler
A, Moser M, Chandraratne S, Von Brühl ML, Lorenz M, Korff T, Rudelius M, Popp
O, Kirchner M, Mertins P, Nimmerjahn F, Iannacone M, Sperandio M, Engelmann B,
Verschoor A, Massberg S. 2024. Antibodies and complement are key drivers of thrombosis.
Immunity. 57(9), 2140–2156.
mla: Stark, Konstantin, et al. “Antibodies and Complement Are Key Drivers of Thrombosis.”
Immunity, vol. 57, no. 9, Elsevier, 2024, pp. 2140–56, doi:10.1016/j.immuni.2024.08.007.
short: K. Stark, B. Kilani, S. Stockhausen, J. Busse, I. Schubert, T.D. Tran, F.R.
Gärtner, A. Leunig, K. Pekayvaz, L. Nicolai, V. Fumagalli, J. Stermann, F. Stephan,
C. David, M.B. Müller, B. Heyman, A. Lux, A. Da Palma Guerreiro, L.P. Frenzel,
C.Q. Schmidt, A. Dopler, M. Moser, S. Chandraratne, M.L. Von Brühl, M. Lorenz,
T. Korff, M. Rudelius, O. Popp, M. Kirchner, P. Mertins, F. Nimmerjahn, M. Iannacone,
M. Sperandio, B. Engelmann, A. Verschoor, S. Massberg, Immunity 57 (2024) 2140–2156.
date_created: 2024-09-22T22:01:42Z
date_published: 2024-09-10T00:00:00Z
date_updated: 2025-09-08T09:50:13Z
day: '10'
ddc:
- '570'
department:
- _id: MiSi
doi: 10.1016/j.immuni.2024.08.007
external_id:
isi:
- '001317438500001'
pmid:
- '39226900'
file:
- access_level: open_access
checksum: 4683de43d06a8fd8e3fc91af4ddc1ba2
content_type: application/pdf
creator: dernst
date_created: 2024-09-30T09:16:03Z
date_updated: 2024-09-30T09:16:03Z
file_id: '18162'
file_name: 2024_Immunity_Stark.pdf
file_size: 6892750
relation: main_file
success: 1
file_date_updated: 2024-09-30T09:16:03Z
has_accepted_license: '1'
intvolume: ' 57'
isi: 1
issue: '9'
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
page: 2140-2156
pmid: 1
publication: Immunity
publication_identifier:
eissn:
- 1097-4180
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Antibodies and complement are key drivers of thrombosis
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: 57
year: '2024'
...
---
_id: '13052'
abstract:
- lang: eng
text: Imaging of the immunological synapse (IS) between dendritic cells (DCs) and
T cells in suspension is hampered by suboptimal alignment of cell-cell contacts
along the vertical imaging plane. This requires optical sectioning that often
results in unsatisfactory resolution in time and space. Here, we present a workflow
where DCs and T cells are confined between a layer of glass and polydimethylsiloxane
(PDMS) that orients the cells along one, horizontal imaging plane, allowing for
fast en-face-imaging of the DC-T cell IS.
acknowledged_ssus:
- _id: Bio
- _id: NanoFab
- _id: M-Shop
acknowledgement: 'A.L. was funded by an Erwin Schrödinger postdoctoral fellowship
of the Austrian Science Fund (FWF, project number: J4542-B) and is an EMBO non-stipendiary
postdoctoral fellow. This work was supported by a European Research Council grant
ERC-CoG-72437 to M.S. We thank the Imaging & Optics facility, the Nanofabrication
facility, and the Miba Machine Shop of ISTA for their excellent support.'
alternative_title:
- Methods in Molecular Biology
article_processing_charge: No
author:
- first_name: Alexander F
full_name: Leithner, Alexander F
id: 3B1B77E4-F248-11E8-B48F-1D18A9856A87
last_name: Leithner
orcid: 0000-0002-1073-744X
- first_name: Jack
full_name: Merrin, Jack
id: 4515C308-F248-11E8-B48F-1D18A9856A87
last_name: Merrin
orcid: 0000-0001-5145-4609
- 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: 'Leithner AF, Merrin J, Sixt MK. En-Face Imaging of T Cell-Dendritic Cell Immunological
Synapses. In: Baldari C, Dustin M, eds. The Immune Synapse. Vol 2654. MIMB.
New York, NY: Springer Nature; 2023:137-147. doi:10.1007/978-1-0716-3135-5_9'
apa: 'Leithner, A. F., Merrin, J., & Sixt, M. K. (2023). En-Face Imaging of
T Cell-Dendritic Cell Immunological Synapses. In C. Baldari & M. Dustin (Eds.),
The Immune Synapse (Vol. 2654, pp. 137–147). New York, NY: Springer Nature.
https://doi.org/10.1007/978-1-0716-3135-5_9'
chicago: 'Leithner, Alexander F, Jack Merrin, and Michael K Sixt. “En-Face Imaging
of T Cell-Dendritic Cell Immunological Synapses.” In The Immune Synapse,
edited by Cosima Baldari and Michael Dustin, 2654:137–47. MIMB. New York, NY:
Springer Nature, 2023. https://doi.org/10.1007/978-1-0716-3135-5_9.'
ieee: 'A. F. Leithner, J. Merrin, and M. K. Sixt, “En-Face Imaging of T Cell-Dendritic
Cell Immunological Synapses,” in The Immune Synapse, vol. 2654, C. Baldari
and M. Dustin, Eds. New York, NY: Springer Nature, 2023, pp. 137–147.'
ista: 'Leithner AF, Merrin J, Sixt MK. 2023.En-Face Imaging of T Cell-Dendritic
Cell Immunological Synapses. In: The Immune Synapse. Methods in Molecular Biology,
vol. 2654, 137–147.'
mla: Leithner, Alexander F., et al. “En-Face Imaging of T Cell-Dendritic Cell Immunological
Synapses.” The Immune Synapse, edited by Cosima Baldari and Michael Dustin,
vol. 2654, Springer Nature, 2023, pp. 137–47, doi:10.1007/978-1-0716-3135-5_9.
short: A.F. Leithner, J. Merrin, M.K. Sixt, in:, C. Baldari, M. Dustin (Eds.), The
Immune Synapse, Springer Nature, New York, NY, 2023, pp. 137–147.
date_created: 2023-05-22T08:41:48Z
date_published: 2023-04-28T00:00:00Z
date_updated: 2025-04-14T07:42:07Z
day: '28'
department:
- _id: MiSi
- _id: NanoFab
doi: 10.1007/978-1-0716-3135-5_9
ec_funded: 1
editor:
- first_name: Cosima
full_name: Baldari, Cosima
last_name: Baldari
- first_name: Michael
full_name: Dustin, Michael
last_name: Dustin
external_id:
pmid:
- '37106180'
intvolume: ' 2654'
language:
- iso: eng
month: '04'
oa_version: None
page: 137-147
place: New York, NY
pmid: 1
project:
- _id: 25FE9508-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '724373'
name: Cellular Navigation Along Spatial Gradients
publication: The Immune Synapse
publication_identifier:
eisbn:
- '9781071631355'
eissn:
- 1940-6029
isbn:
- '9781071631348'
issn:
- 1064-3745
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
series_title: MIMB
status: public
title: En-Face Imaging of T Cell-Dendritic Cell Immunological Synapses
type: book_chapter
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 2654
year: '2023'
...
---
_id: '14361'
abstract:
- lang: eng
text: Whether one considers swarming insects, flocking birds, or bacterial colonies,
collective motion arises from the coordination of individuals and entails the
adjustment of their respective velocities. In particular, in close confinements,
such as those encountered by dense cell populations during development or regeneration,
collective migration can only arise coordinately. Yet, how individuals unify their
velocities is often not understood. Focusing on a finite number of cells in circular
confinements, we identify waves of polymerizing actin that function as a pacemaker
governing the speed of individual cells. We show that the onset of collective
motion coincides with the synchronization of the wave nucleation frequencies across
the population. Employing a simpler and more readily accessible mechanical model
system of active spheres, we identify the synchronization of the individuals’
internal oscillators as one of the essential requirements to reach the corresponding
collective state. The mechanical ‘toy’ experiment illustrates that the global
synchronous state is achieved by nearest neighbor coupling. We suggest by analogy
that local coupling and the synchronization of actin waves are essential for the
emergent, self-organized motion of cell collectives.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: M-Shop
acknowledgement: We thank K. O’Keeffe, E. Hannezo, P. Devreotes, C. Dessalles, and
E. Martens for discussion and/or critical reading of the manuscript; the Bioimaging
Facility of ISTA for excellent support, as well as the Life Science Facility and
the Miba Machine Shop of ISTA. This work was supported by the European Research
Council (ERC StG 281556 and CoG 724373) to M.S.
article_number: '5633'
article_processing_charge: Yes
article_type: original
author:
- first_name: Michael
full_name: Riedl, Michael
id: 3BE60946-F248-11E8-B48F-1D18A9856A87
last_name: Riedl
orcid: 0000-0003-4844-6311
- first_name: Isabelle D
full_name: Mayer, Isabelle D
id: 61763940-15b2-11ec-abd3-cfaddfbc66b4
last_name: Mayer
- first_name: Jack
full_name: Merrin, Jack
id: 4515C308-F248-11E8-B48F-1D18A9856A87
last_name: Merrin
orcid: 0000-0001-5145-4609
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
- first_name: Björn
full_name: Hof, Björn
id: 3A374330-F248-11E8-B48F-1D18A9856A87
last_name: Hof
orcid: 0000-0003-2057-2754
citation:
ama: Riedl M, Mayer ID, Merrin J, Sixt MK, Hof B. Synchronization in collectively
moving inanimate and living active matter. Nature Communications. 2023;14.
doi:10.1038/s41467-023-41432-1
apa: Riedl, M., Mayer, I. D., Merrin, J., Sixt, M. K., & Hof, B. (2023). Synchronization
in collectively moving inanimate and living active matter. Nature Communications.
Springer Nature. https://doi.org/10.1038/s41467-023-41432-1
chicago: Riedl, Michael, Isabelle D Mayer, Jack Merrin, Michael K Sixt, and Björn
Hof. “Synchronization in Collectively Moving Inanimate and Living Active Matter.”
Nature Communications. Springer Nature, 2023. https://doi.org/10.1038/s41467-023-41432-1.
ieee: M. Riedl, I. D. Mayer, J. Merrin, M. K. Sixt, and B. Hof, “Synchronization
in collectively moving inanimate and living active matter,” Nature Communications,
vol. 14. Springer Nature, 2023.
ista: Riedl M, Mayer ID, Merrin J, Sixt MK, Hof B. 2023. Synchronization in collectively
moving inanimate and living active matter. Nature Communications. 14, 5633.
mla: Riedl, Michael, et al. “Synchronization in Collectively Moving Inanimate and
Living Active Matter.” Nature Communications, vol. 14, 5633, Springer Nature,
2023, doi:10.1038/s41467-023-41432-1.
short: M. Riedl, I.D. Mayer, J. Merrin, M.K. Sixt, B. Hof, Nature Communications
14 (2023).
corr_author: '1'
date_created: 2023-09-24T22:01:10Z
date_published: 2023-09-13T00:00:00Z
date_updated: 2025-04-14T13:10:03Z
day: '13'
ddc:
- '530'
- '570'
department:
- _id: MiSi
- _id: NanoFab
- _id: BjHo
doi: 10.1038/s41467-023-41432-1
ec_funded: 1
external_id:
isi:
- '001087583700030'
pmid:
- '37704595'
file:
- access_level: open_access
checksum: 82d2d4ad736cc8493db8ce45cd313f7b
content_type: application/pdf
creator: dernst
date_created: 2023-09-25T08:32:37Z
date_updated: 2023-09-25T08:32:37Z
file_id: '14366'
file_name: 2023_NatureComm_Riedl.pdf
file_size: 2317272
relation: main_file
success: 1
file_date_updated: 2023-09-25T08:32:37Z
has_accepted_license: '1'
intvolume: ' 14'
isi: 1
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 25A603A2-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '281556'
name: Cytoskeletal force generation and force transduction of migrating leukocytes
- _id: 25FE9508-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '724373'
name: Cellular Navigation Along Spatial Gradients
publication: Nature Communications
publication_identifier:
eissn:
- 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Synchronization in collectively moving inanimate and living active matter
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'
...
---
OA_place: publisher
_id: '14530'
abstract:
- lang: eng
text: 'Most motions of many-body systems at any scale in nature with sufficient
degrees of freedom tend to be chaotic; reaching from the orbital motion of planets,
the air currents in our atmosphere, down to the water flowing through our pipelines
or the movement of a population of bacteria. To the observer it is therefore intriguing
when a moving collective exhibits order. Collective motion of flocks of birds,
schools of fish or swarms of self-propelled particles or robots have been studied
extensively over the past decades but the mechanisms involved in the transition
from chaos to order remain unclear. Here, the interactions, that in most systems
give rise to chaos, sustain order. In this thesis we investigate mechanisms that
preserve, destabilize or lead to the ordered state. We show that endothelial cells
migrating in circular confinements transition to a collective rotating state and
concomitantly synchronize the frequencies of nucleating actin waves within individual
cells. Consequently, the frequency dependent cell migration speed uniformizes
across the population. Complementary to the WAVE dependent nucleation of traveling
actin waves, we show that in leukocytes the actin polymerization depending on
WASp generates pushing forces locally at stationary patches. Next, in pipe flows,
we study methods to disrupt the self--sustaining cycle of turbulence and therefore
relaminarize the flow. While we find in pulsating flow conditions that turbulence
emerges through a helical instability during the decelerating phase. Finally,
we show quantitatively in brain slices of mice that wild-type control neurons
can compensate the migratory deficits of a genetically modified neuronal sub--population
in the developing cortex. '
acknowledged_ssus:
- _id: M-Shop
- _id: Bio
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Michael
full_name: Riedl, Michael
id: 3BE60946-F248-11E8-B48F-1D18A9856A87
last_name: Riedl
orcid: 0000-0003-4844-6311
citation:
ama: Riedl M. Synchronization in collectively moving active matter. 2023. doi:10.15479/14530
apa: Riedl, M. (2023). Synchronization in collectively moving active matter.
Institute of Science and Technology Austria. https://doi.org/10.15479/14530
chicago: Riedl, Michael. “Synchronization in Collectively Moving Active Matter.”
Institute of Science and Technology Austria, 2023. https://doi.org/10.15479/14530.
ieee: M. Riedl, “Synchronization in collectively moving active matter,” Institute
of Science and Technology Austria, 2023.
ista: Riedl M. 2023. Synchronization in collectively moving active matter. Institute
of Science and Technology Austria.
mla: Riedl, Michael. Synchronization in Collectively Moving Active Matter.
Institute of Science and Technology Austria, 2023, doi:10.15479/14530.
short: M. Riedl, Synchronization in Collectively Moving Active Matter, Institute
of Science and Technology Austria, 2023.
corr_author: '1'
date_created: 2023-11-15T09:59:03Z
date_published: 2023-11-16T00:00:00Z
date_updated: 2026-04-07T13:29:13Z
day: '16'
ddc:
- '530'
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: MiSi
doi: 10.15479/14530
file:
- access_level: open_access
checksum: 52e1d0ab6c1abe59c82dfe8c9ff5f83a
content_type: application/pdf
creator: mriedl
date_created: 2023-11-15T09:52:54Z
date_updated: 2023-11-15T09:52:54Z
file_id: '14536'
file_name: Thesis_Riedl_2023_corr.pdf
file_size: 36743942
relation: main_file
success: 1
file_date_updated: 2023-11-15T09:52:54Z
has_accepted_license: '1'
keyword:
- Synchronization
- Collective Movement
- Active Matter
- Cell Migration
- Active Colloids
language:
- iso: eng
month: '11'
oa: 1
oa_version: Updated Version
page: '260'
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '461'
relation: part_of_dissertation
status: public
- id: '10791'
relation: part_of_dissertation
status: public
- id: '7932'
relation: part_of_dissertation
status: public
- id: '10703'
relation: part_of_dissertation
status: public
- id: '12726'
relation: old_edition
status: public
status: public
supervisor:
- first_name: Björn
full_name: Hof, Björn
id: 3A374330-F248-11E8-B48F-1D18A9856A87
last_name: Hof
orcid: 0000-0003-2057-2754
title: Synchronization in collectively moving active matter
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2023'
...
---
_id: '14555'
abstract:
- lang: eng
text: The intricate regulatory processes behind actin polymerization play a crucial
role in cellular biology, including essential mechanisms such as cell migration
or cell division. However, the self-organizing principles governing actin polymerization
are still poorly understood. In this perspective article, we compare the Belousov-Zhabotinsky
(BZ) reaction, a classic and well understood chemical oscillator known for its
self-organizing spatiotemporal dynamics, with the excitable dynamics of polymerizing
actin. While the BZ reaction originates from the domain of inorganic chemistry,
it shares remarkable similarities with actin polymerization, including the characteristic
propagating waves, which are influenced by geometry and external fields, and the
emergent collective behavior. Starting with a general description of emerging
patterns, we elaborate on single droplets or cell-level dynamics, the influence
of geometric confinements and conclude with collective interactions. Comparing
these two systems sheds light on the universal nature of self-organization principles
in both living and inanimate systems.
acknowledgement: The author(s) declare that no financial support was received for
the research, authorship, and/or publication of this article.
article_number: '1287420'
article_processing_charge: Yes
article_type: original
author:
- first_name: Michael
full_name: Riedl, Michael
id: 3BE60946-F248-11E8-B48F-1D18A9856A87
last_name: Riedl
orcid: 0000-0003-4844-6311
- 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: Riedl M, Sixt MK. The excitable nature of polymerizing actin and the Belousov-Zhabotinsky
reaction. Frontiers in Cell and Developmental Biology. 2023;11. doi:10.3389/fcell.2023.1287420
apa: Riedl, M., & Sixt, M. K. (2023). The excitable nature of polymerizing actin
and the Belousov-Zhabotinsky reaction. Frontiers in Cell and Developmental
Biology. Frontiers. https://doi.org/10.3389/fcell.2023.1287420
chicago: Riedl, Michael, and Michael K Sixt. “The Excitable Nature of Polymerizing
Actin and the Belousov-Zhabotinsky Reaction.” Frontiers in Cell and Developmental
Biology. Frontiers, 2023. https://doi.org/10.3389/fcell.2023.1287420.
ieee: M. Riedl and M. K. Sixt, “The excitable nature of polymerizing actin and the
Belousov-Zhabotinsky reaction,” Frontiers in Cell and Developmental Biology,
vol. 11. Frontiers, 2023.
ista: Riedl M, Sixt MK. 2023. The excitable nature of polymerizing actin and the
Belousov-Zhabotinsky reaction. Frontiers in Cell and Developmental Biology. 11,
1287420.
mla: Riedl, Michael, and Michael K. Sixt. “The Excitable Nature of Polymerizing
Actin and the Belousov-Zhabotinsky Reaction.” Frontiers in Cell and Developmental
Biology, vol. 11, 1287420, Frontiers, 2023, doi:10.3389/fcell.2023.1287420.
short: M. Riedl, M.K. Sixt, Frontiers in Cell and Developmental Biology 11 (2023).
corr_author: '1'
date_created: 2023-11-19T23:00:55Z
date_published: 2023-10-31T00:00:00Z
date_updated: 2025-09-09T13:22:00Z
day: '31'
ddc:
- '570'
department:
- _id: MiSi
doi: 10.3389/fcell.2023.1287420
external_id:
isi:
- '001100762800001'
pmid:
- '38020899'
file:
- access_level: open_access
checksum: 61857fc3ebf019354932e7ee684658ce
content_type: application/pdf
creator: dernst
date_created: 2023-11-20T08:41:15Z
date_updated: 2023-11-20T08:41:15Z
file_id: '14561'
file_name: 2023_FrontiersCellDevBio_Riedl.pdf
file_size: 2047622
relation: main_file
success: 1
file_date_updated: 2023-11-20T08:41:15Z
has_accepted_license: '1'
intvolume: ' 11'
isi: 1
language:
- iso: eng
month: '10'
oa: 1
oa_version: Published Version
pmid: 1
publication: Frontiers in Cell and Developmental Biology
publication_identifier:
eissn:
- 2296-634X
publication_status: published
publisher: Frontiers
quality_controlled: '1'
scopus_import: '1'
status: public
title: The excitable nature of polymerizing actin and the Belousov-Zhabotinsky reaction
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: 11
year: '2023'
...
---
_id: '14848'
abstract:
- lang: eng
text: Regulating protein states is considered the core function of chaperones. However,
despite their importance to all major cellular processes, the conformational changes
that chaperones impart on polypeptide chains are difficult to study directly due
to their heterogeneous, dynamic, and multi-step nature. Here, we review recent
advances towards this aim using single-molecule manipulation methods, which are
rapidly revealing new mechanisms of conformational control and helping to define
a different perspective on the chaperone function.
alternative_title:
- New Developments in NMR
article_processing_charge: No
author:
- first_name: F.
full_name: Wruck, F.
last_name: Wruck
- first_name: Mario
full_name: Avellaneda Sarrió, Mario
id: DC4BA84C-56E6-11EA-AD5D-348C3DDC885E
last_name: Avellaneda Sarrió
orcid: 0000-0001-6406-524X
- first_name: M. M.
full_name: Naqvi, M. M.
last_name: Naqvi
- first_name: E. J.
full_name: Koers, E. J.
last_name: Koers
- first_name: K.
full_name: Till, K.
last_name: Till
- first_name: L.
full_name: Gross, L.
last_name: Gross
- first_name: F.
full_name: Moayed, F.
last_name: Moayed
- first_name: A.
full_name: Roland, A.
last_name: Roland
- first_name: L. W. H. J.
full_name: Heling, L. W. H. J.
last_name: Heling
- first_name: A.
full_name: Mashaghi, A.
last_name: Mashaghi
- first_name: S. J.
full_name: Tans, S. J.
last_name: Tans
citation:
ama: 'Wruck F, Avellaneda Sarrió M, Naqvi MM, et al. Probing Single Chaperone Substrates.
In: Hiller S, Liu M, He L, eds. Biophysics of Molecular Chaperones. Vol
29. Royal Society of Chemistry; 2023:278-318. doi:10.1039/bk9781839165986-00278'
apa: Wruck, F., Avellaneda Sarrió, M., Naqvi, M. M., Koers, E. J., Till, K., Gross,
L., … Tans, S. J. (2023). Probing Single Chaperone Substrates. In S. Hiller, M.
Liu, & L. He (Eds.), Biophysics of Molecular Chaperones (Vol. 29, pp.
278–318). Royal Society of Chemistry. https://doi.org/10.1039/bk9781839165986-00278
chicago: Wruck, F., Mario Avellaneda Sarrió, M. M. Naqvi, E. J. Koers, K. Till,
L. Gross, F. Moayed, et al. “Probing Single Chaperone Substrates.” In Biophysics
of Molecular Chaperones, edited by Sebastian Hiller, Maili Liu, and Lichun
He, 29:278–318. Royal Society of Chemistry, 2023. https://doi.org/10.1039/bk9781839165986-00278.
ieee: F. Wruck et al., “Probing Single Chaperone Substrates,” in Biophysics
of Molecular Chaperones, vol. 29, S. Hiller, M. Liu, and L. He, Eds. Royal
Society of Chemistry, 2023, pp. 278–318.
ista: 'Wruck F, Avellaneda Sarrió M, Naqvi MM, Koers EJ, Till K, Gross L, Moayed
F, Roland A, Heling LWHJ, Mashaghi A, Tans SJ. 2023.Probing Single Chaperone Substrates.
In: Biophysics of Molecular Chaperones. New Developments in NMR, vol. 29, 278–318.'
mla: Wruck, F., et al. “Probing Single Chaperone Substrates.” Biophysics of Molecular
Chaperones, edited by Sebastian Hiller et al., vol. 29, Royal Society of Chemistry,
2023, pp. 278–318, doi:10.1039/bk9781839165986-00278.
short: F. Wruck, M. Avellaneda Sarrió, M.M. Naqvi, E.J. Koers, K. Till, L. Gross,
F. Moayed, A. Roland, L.W.H.J. Heling, A. Mashaghi, S.J. Tans, in:, S. Hiller,
M. Liu, L. He (Eds.), Biophysics of Molecular Chaperones, Royal Society of Chemistry,
2023, pp. 278–318.
date_created: 2024-01-22T08:07:02Z
date_published: 2023-11-01T00:00:00Z
date_updated: 2024-01-23T12:01:53Z
day: '01'
department:
- _id: MiSi
doi: 10.1039/bk9781839165986-00278
editor:
- first_name: Sebastian
full_name: Hiller, Sebastian
last_name: Hiller
- first_name: Maili
full_name: Liu, Maili
last_name: Liu
- first_name: Lichun
full_name: He, Lichun
last_name: He
intvolume: ' 29'
language:
- iso: eng
month: '11'
oa_version: None
page: 278-318
publication: Biophysics of Molecular Chaperones
publication_identifier:
eisbn:
- '9781839165993'
isbn:
- '9781839162824'
publication_status: published
publisher: Royal Society of Chemistry
quality_controlled: '1'
status: public
title: Probing Single Chaperone Substrates
type: book_chapter
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 29
year: '2023'
...
---
OA_place: publisher
_id: '14697'
abstract:
- lang: eng
text: "During my Ph.D. research, I managed a series of projects, each focused on
the\r\nmechanisms underlying cell migration. My work involved an in-depth examination
of\r\nthe complex strategies employed by neutrophils, with a specific focus on
their ability to\r\nsynchronize spatial-temporal cues and optimize their gradient
perception. However, it\r\nis essential to acknowledge that not all projects yielded
successful results, as some\r\nideas were discontinued and are archived for future
reference within this thesis.\r\nMy main project investigated how neutrophils
decode spatial cues for precise navigation. Human neutrophils showcased distinct
movement patterns based on source\r\ntype – linear or point-like. By combining
single-cell tracking in 3D environments with\r\nproxy dyes, this project linked
cell behaviors to gradient changes, revealing a stronger\r\nresponse to semi-exponential
gradients from point sources. In addition, neutrophils\r\nexhibited oscillating
migration speeds, using speed minima to adjust trajectories toward sources. Experiencing
continuous concentration changes, they accelerated over\r\ntime and employed a
\"Run and Fumble\" strategy, alternating between consistent runs\r\nand strategic
\"tumbles\" for efficient navigation.\r\nThe project extended to the possibility
of cells amplifying perceived gradients by\r\nenclosing their immediate surroundings,
pushing attractants forward for enrichment\r\nwhile depleting it at the cell rear.
Microfluidic devices were employed, and various experimental parameters configurations
were optimized. Although significant differences\r\nin migratory efficacy were
detected across pore sizes and device heights, quantifying\r\ngradient manipulation
effects proved challenging.\r\nThe \"Laser-Assisted Protein Adsorption by Photobleaching\"
(LAPAP) project was\r\npromising, as it allowed the printing of gradients. Initially
successful with dendritic cells,\r\nwe aimed to adapt it for neutrophils. Through
extensive experimentation with multiple\r\nparameters, we attempted to trigger
responses from neutrophils. Despite these efforts\r\nand collaboration, the project
failed due to practical challenges and limitations.\r\nFacing a lack of neutrophil-like
cells at IST, we initially established the SCF-HoxB8\r\nprimary murine cell line.
Despite their existence, their migratory behavior was largely\r\nunexplored due
to potential limitations. Through differentiation protocol refinements we\r\nenhanced
their migratory capabilities, though their capacity still lagged behind human\r\nneutrophils.
Despite this, the improved migration potential of these cells pointed toward\r\ntheir
utility for in vitro murine neutrophil migration studies."
acknowledged_ssus:
- _id: LifeSc
- _id: Bio
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Julian A
full_name: Stopp, Julian A
id: 489E3F00-F248-11E8-B48F-1D18A9856A87
last_name: Stopp
citation:
ama: 'Stopp JA. Neutrophils on the hunt : Migratory strategies employed by neutrophils
to fulfill their effector function. 2023. doi:10.15479/at:ista:14697'
apa: 'Stopp, J. A. (2023). Neutrophils on the hunt : Migratory strategies employed
by neutrophils to fulfill their effector function. Institute of Science and
Technology Austria. https://doi.org/10.15479/at:ista:14697'
chicago: 'Stopp, Julian A. “Neutrophils on the Hunt : Migratory Strategies Employed
by Neutrophils to Fulfill Their Effector Function.” Institute of Science and Technology
Austria, 2023. https://doi.org/10.15479/at:ista:14697.'
ieee: 'J. A. Stopp, “Neutrophils on the hunt : Migratory strategies employed by
neutrophils to fulfill their effector function,” Institute of Science and Technology
Austria, 2023.'
ista: 'Stopp JA. 2023. Neutrophils on the hunt : Migratory strategies employed by
neutrophils to fulfill their effector function. Institute of Science and Technology
Austria.'
mla: 'Stopp, Julian A. Neutrophils on the Hunt : Migratory Strategies Employed
by Neutrophils to Fulfill Their Effector Function. Institute of Science and
Technology Austria, 2023, doi:10.15479/at:ista:14697.'
short: 'J.A. Stopp, Neutrophils on the Hunt : Migratory Strategies Employed by Neutrophils
to Fulfill Their Effector Function, Institute of Science and Technology Austria,
2023.'
corr_author: '1'
date_created: 2023-12-18T19:14:28Z
date_published: 2023-12-20T00:00:00Z
date_updated: 2026-06-18T17:34:48Z
day: '20'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: MiSi
doi: 10.15479/at:ista:14697
ec_funded: 1
file:
- access_level: open_access
checksum: 457927165d5d556305d3086f6b83e5c7
content_type: application/pdf
creator: jstopp
date_created: 2023-12-20T09:35:34Z
date_updated: 2024-12-20T23:30:04Z
embargo: 2024-12-20
file_id: '14699'
file_name: Thesis.pdf
file_size: 51585778
relation: main_file
- access_level: closed
checksum: e8d26449ac461f5e8478a62c9507506f
content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
creator: jstopp
date_created: 2023-12-20T09:35:35Z
date_updated: 2024-12-20T23:30:04Z
embargo_to: open_access
file_id: '14700'
file_name: Thesis.docx
file_size: 69625950
relation: source_file
file_date_updated: 2024-12-20T23:30:04Z
has_accepted_license: '1'
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
page: '226'
project:
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '665385'
name: International IST Doctoral Program
publication_identifier:
isbn:
- 978-3-99078-038-1
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '14360'
relation: part_of_dissertation
status: public
- id: '12272'
relation: part_of_dissertation
status: public
- id: '6328'
relation: part_of_dissertation
status: public
- id: '7885'
relation: part_of_dissertation
status: public
- id: '14274'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
title: 'Neutrophils on the hunt : Migratory strategies employed by neutrophils to
fulfill their effector function'
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2023'
...
---
_id: '14360'
abstract:
- lang: eng
text: To navigate through diverse tissues, migrating cells must balance persistent
self-propelled motion with adaptive behaviors to circumvent obstacles. We identify
a curvature-sensing mechanism underlying obstacle evasion in immune-like cells.
Specifically, we propose that actin polymerization at the advancing edge of migrating
cells is inhibited by the curvature-sensitive BAR domain protein Snx33 in regions
with inward plasma membrane curvature. The genetic perturbation of this machinery
reduces the cells’ capacity to evade obstructions combined with faster and more
persistent cell migration in obstacle-free environments. Our results show how
cells can read out their surface topography and utilize actin and plasma membrane
biophysics to interpret their environment, allowing them to adaptively decide
if they should move ahead or turn away. On the basis of our findings, we propose
that the natural diversity of BAR domain proteins may allow cells to tune their
curvature sensing machinery to match the shape characteristics in their environment.
acknowledgement: "We thank Jan Ellenberg, Leanne Strauss, Anusha Gopalan, and Jia
Hui Li for critical feedback on the manuscript and the Life Science Editors for
editing assistance. The plasmid with hSnx33 was a kind gift from Duanqing Pei. Cell
line with GFP-tagged IRSp53 was a kind gift from Orion Weiner. We thank Brian Graziano
for providing protocols, reagents, and key advice to generate CRISPR knockout HL-60
cells. We thank the EMBL flow cytometry core facility, the EMBL advanced light microscopy
facility, the EMBL proteomics facility, and the EMBL genomics core facility for
support and advice. We thank Anusha Gopalan and Martin Bergert for their support
during mechanical measurements by AFM. We thank Estela Sosa Osorio for technical
assistance for the co-immunoprecipitation. We thank the EMBL genome biology computational
support (and specially Charles Girardot and Jelle Scholtalbers) for critical assistance
during RNAseq analysis. We thank Hans Kristian Hannibal‐Bach for his technical assistance
during the lipidomic analysis of plasma membrane isolates. We thank Steffen Burgold
for their support with LLS7 microscope in the ZEISS Microscopy Customer Center Europe.
We acknowledge the financial support of the European Molecular Biology Laboratory
(EMBL) to A.D.-M., Y.S., A.K., and A.E., the EMBL Interdisciplinary Postdocs (EIPOD)
program under Marie Sklodowska-Curie COFUND actions MSCA-COFUND-FP to M.S.B. and
M. S. (grant agreement number: 847543), the BEST program funding by FCT (SFRH/BEST/150300/2019)
to S.D.A. and the Joachim Herz Stiftung Add-on Fellowship for Interdisciplinary
Science to E.S.\r\nOpen Access funding enabled and organized by Projekt DEAL."
article_number: '5644'
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Ewa
full_name: Sitarska, Ewa
last_name: Sitarska
- first_name: Silvia Dias
full_name: Almeida, Silvia Dias
last_name: Almeida
- first_name: Marianne Sandvold
full_name: Beckwith, Marianne Sandvold
last_name: Beckwith
- first_name: Julian A
full_name: Stopp, Julian A
id: 489E3F00-F248-11E8-B48F-1D18A9856A87
last_name: Stopp
- first_name: Jakub
full_name: Czuchnowski, Jakub
last_name: Czuchnowski
- first_name: Marc
full_name: Siggel, Marc
last_name: Siggel
- first_name: Rita
full_name: Roessner, Rita
last_name: Roessner
- first_name: Aline
full_name: Tschanz, Aline
last_name: Tschanz
- first_name: Christer
full_name: Ejsing, Christer
last_name: Ejsing
- first_name: Yannick
full_name: Schwab, Yannick
last_name: Schwab
- first_name: Jan
full_name: Kosinski, Jan
last_name: Kosinski
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
- first_name: Anna
full_name: Kreshuk, Anna
last_name: Kreshuk
- first_name: Anna
full_name: Erzberger, Anna
last_name: Erzberger
- first_name: Alba
full_name: Diz-Muñoz, Alba
last_name: Diz-Muñoz
citation:
ama: Sitarska E, Almeida SD, Beckwith MS, et al. Sensing their plasma membrane curvature
allows migrating cells to circumvent obstacles. Nature Communications.
2023;14. doi:10.1038/s41467-023-41173-1
apa: Sitarska, E., Almeida, S. D., Beckwith, M. S., Stopp, J. A., Czuchnowski, J.,
Siggel, M., … Diz-Muñoz, A. (2023). Sensing their plasma membrane curvature allows
migrating cells to circumvent obstacles. Nature Communications. Springer
Nature. https://doi.org/10.1038/s41467-023-41173-1
chicago: Sitarska, Ewa, Silvia Dias Almeida, Marianne Sandvold Beckwith, Julian
A Stopp, Jakub Czuchnowski, Marc Siggel, Rita Roessner, et al. “Sensing Their
Plasma Membrane Curvature Allows Migrating Cells to Circumvent Obstacles.” Nature
Communications. Springer Nature, 2023. https://doi.org/10.1038/s41467-023-41173-1.
ieee: E. Sitarska et al., “Sensing their plasma membrane curvature allows
migrating cells to circumvent obstacles,” Nature Communications, vol. 14.
Springer Nature, 2023.
ista: Sitarska E, Almeida SD, Beckwith MS, Stopp JA, Czuchnowski J, Siggel M, Roessner
R, Tschanz A, Ejsing C, Schwab Y, Kosinski J, Sixt MK, Kreshuk A, Erzberger A,
Diz-Muñoz A. 2023. Sensing their plasma membrane curvature allows migrating cells
to circumvent obstacles. Nature Communications. 14, 5644.
mla: Sitarska, Ewa, et al. “Sensing Their Plasma Membrane Curvature Allows Migrating
Cells to Circumvent Obstacles.” Nature Communications, vol. 14, 5644, Springer
Nature, 2023, doi:10.1038/s41467-023-41173-1.
short: E. Sitarska, S.D. Almeida, M.S. Beckwith, J.A. Stopp, J. Czuchnowski, M.
Siggel, R. Roessner, A. Tschanz, C. Ejsing, Y. Schwab, J. Kosinski, M.K. Sixt,
A. Kreshuk, A. Erzberger, A. Diz-Muñoz, Nature Communications 14 (2023).
date_created: 2023-09-24T22:01:10Z
date_published: 2023-09-13T00:00:00Z
date_updated: 2026-06-24T22:30:20Z
day: '13'
ddc:
- '570'
department:
- _id: MiSi
doi: 10.1038/s41467-023-41173-1
external_id:
isi:
- '001087583700008'
pmid:
- '37704612'
file:
- access_level: open_access
checksum: ad670e3b3c64fc585675948370f6b149
content_type: application/pdf
creator: dernst
date_created: 2023-09-25T08:22:58Z
date_updated: 2023-09-25T08:22:58Z
file_id: '14365'
file_name: 2023_NatureComm_Sitarska.pdf
file_size: 2725421
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file_date_updated: 2023-09-25T08:22:58Z
has_accepted_license: '1'
intvolume: ' 14'
isi: 1
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
pmid: 1
publication: Nature Communications
publication_identifier:
eissn:
- 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
record:
- id: '14697'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Sensing their plasma membrane curvature allows migrating cells to circumvent
obstacles
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: '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. Science Immunology.
2023;8(87). doi:10.1126/sciimmunol.adc9584
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. Science Immunology. American Association
for the Advancement of Science. https://doi.org/10.1126/sciimmunol.adc9584
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.” Science
Immunology. American Association for the Advancement of Science, 2023. https://doi.org/10.1126/sciimmunol.adc9584.
ieee: J. H. Alanko et al., “CCR7 acts as both a sensor and a sink for CCL19
to coordinate collective leukocyte migration,” Science Immunology, 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.” Science Immunology, vol. 8,
no. 87, adc9584, American Association for the Advancement of Science, 2023, doi:10.1126/sciimmunol.adc9584.
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: 2026-06-24T22:30:32Z
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'
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'
relation: research_data
status: public
- id: '14697'
relation: dissertation_contains
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: '11588'
abstract:
- lang: eng
text: Visualizing cell behavior and effector function on a single cell level has
been crucial for understanding key aspects of mammalian biology. Due to their
small size, large number and rapid recruitment into thrombi, there is a lack of
data on fate and behavior of individual platelets in thrombosis and hemostasis.
Here we report the use of platelet lineage restricted multi-color reporter mouse
strains to delineate platelet function on a single cell level. We show that genetic
labeling allows for single platelet and megakaryocyte (MK) tracking and morphological
analysis in vivo and in vitro, while not affecting lineage functions. Using Cre-driven
Confetti expression, we provide insights into temporal gene expression patterns
as well as spatial clustering of MK in the bone marrow. In the vasculature, shape
analysis of activated platelets recruited to thrombi identifies ubiquitous filopodia
formation with no evidence of lamellipodia formation. Single cell tracking in
complex thrombi reveals prominent myosin-dependent motility of platelets and highlights
thrombus formation as a highly dynamic process amenable to modification and intervention
of the acto-myosin cytoskeleton. Platelet function assays combining flow cytrometry,
as well as in vivo, ex vivo and in vitro imaging show unaltered platelet functions
of multicolor reporter mice compared to wild-type controls. In conclusion, platelet
lineage multicolor reporter mice prove useful in furthering our understanding
of platelet and MK biology on a single cell level.
acknowledgement: "This study was supported by the Deutsche Forschungsgemeinschaft
(DFG) SFB 914 ( to SM [B02 and Z01]), the DFG SFB 1123 (to SM [B06]), the DFG FOR
2033 (to SM), the German\r\nCenter for Cardiovascular Research (DZHK) (Clinician
Scientist Programme), MHA 1.4VD (to SM), Postdoc Start-up Grant, 81X3600213 (to
FG), 81X3600222 (to LN), the FP7 program\r\n(project 260309, PRESTIGE [to SM]).
This project has received funding from the European Research Council (ERC) under
the European Union’s Horizon 2020 research and innovation programme (grant agreement
No. 83344, ERC-2018-ADG “IMMUNOTHROMBOSIS” [to SM] and the Marie Skłodowska Curie
Individual Fellowship (EU project 747687, LamelliActin [to FG]). "
article_processing_charge: No
article_type: original
author:
- first_name: Leo
full_name: Nicolai, Leo
last_name: Nicolai
- first_name: Rainer
full_name: Kaiser, Rainer
last_name: Kaiser
- first_name: Raphael
full_name: Escaig, Raphael
last_name: Escaig
- first_name: Marie Louise
full_name: Hoffknecht, Marie Louise
last_name: Hoffknecht
- first_name: Afra
full_name: Anjum, Afra
last_name: Anjum
- first_name: Alexander
full_name: Leunig, Alexander
last_name: Leunig
- first_name: Joachim
full_name: Pircher, Joachim
last_name: Pircher
- first_name: Andreas
full_name: Ehrlich, Andreas
last_name: Ehrlich
- first_name: Michael
full_name: Lorenz, Michael
last_name: Lorenz
- first_name: Hellen
full_name: Ishikawa-Ankerhold, Hellen
last_name: Ishikawa-Ankerhold
- first_name: William C.
full_name: Aird, William C.
last_name: Aird
- first_name: Steffen
full_name: Massberg, Steffen
last_name: Massberg
- first_name: Florian R
full_name: Gärtner, Florian R
id: 397A88EE-F248-11E8-B48F-1D18A9856A87
last_name: Gärtner
orcid: 0000-0001-6120-3723
citation:
ama: Nicolai L, Kaiser R, Escaig R, et al. Single platelet and megakaryocyte morpho-dynamics
uncovered by multicolor reporter mouse strains in vitro and in vivo. Haematologica.
2022;107(7):1669-1680. doi:10.3324/haematol.2021.278896
apa: Nicolai, L., Kaiser, R., Escaig, R., Hoffknecht, M. L., Anjum, A., Leunig,
A., … Gärtner, F. R. (2022). Single platelet and megakaryocyte morpho-dynamics
uncovered by multicolor reporter mouse strains in vitro and in vivo. Haematologica.
Ferrata Storti Foundation. https://doi.org/10.3324/haematol.2021.278896
chicago: Nicolai, Leo, Rainer Kaiser, Raphael Escaig, Marie Louise Hoffknecht, Afra
Anjum, Alexander Leunig, Joachim Pircher, et al. “Single Platelet and Megakaryocyte
Morpho-Dynamics Uncovered by Multicolor Reporter Mouse Strains in Vitro and in
Vivo.” Haematologica. Ferrata Storti Foundation, 2022. https://doi.org/10.3324/haematol.2021.278896.
ieee: L. Nicolai et al., “Single platelet and megakaryocyte morpho-dynamics
uncovered by multicolor reporter mouse strains in vitro and in vivo,” Haematologica,
vol. 107, no. 7. Ferrata Storti Foundation, pp. 1669–1680, 2022.
ista: Nicolai L, Kaiser R, Escaig R, Hoffknecht ML, Anjum A, Leunig A, Pircher J,
Ehrlich A, Lorenz M, Ishikawa-Ankerhold H, Aird WC, Massberg S, Gärtner FR. 2022.
Single platelet and megakaryocyte morpho-dynamics uncovered by multicolor reporter
mouse strains in vitro and in vivo. Haematologica. 107(7), 1669–1680.
mla: Nicolai, Leo, et al. “Single Platelet and Megakaryocyte Morpho-Dynamics Uncovered
by Multicolor Reporter Mouse Strains in Vitro and in Vivo.” Haematologica,
vol. 107, no. 7, Ferrata Storti Foundation, 2022, pp. 1669–80, doi:10.3324/haematol.2021.278896.
short: L. Nicolai, R. Kaiser, R. Escaig, M.L. Hoffknecht, A. Anjum, A. Leunig, J.
Pircher, A. Ehrlich, M. Lorenz, H. Ishikawa-Ankerhold, W.C. Aird, S. Massberg,
F.R. Gärtner, Haematologica 107 (2022) 1669–1680.
corr_author: '1'
date_created: 2022-07-17T22:01:54Z
date_published: 2022-07-01T00:00:00Z
date_updated: 2025-04-14T07:43:16Z
day: '01'
ddc:
- '570'
department:
- _id: MiSi
doi: 10.3324/haematol.2021.278896
ec_funded: 1
external_id:
isi:
- '000823746100018'
file:
- access_level: open_access
checksum: 9b47830945f3c30428fe9cfee2dc4a8a
content_type: application/pdf
creator: dernst
date_created: 2022-07-18T07:51:55Z
date_updated: 2022-07-18T07:51:55Z
file_id: '11595'
file_name: 2022_Haematologica_Nicolai.pdf
file_size: 1722094
relation: main_file
success: 1
file_date_updated: 2022-07-18T07:51:55Z
has_accepted_license: '1'
intvolume: ' 107'
isi: 1
issue: '7'
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc/4.0/
month: '07'
oa: 1
oa_version: Published Version
page: 1669-1680
project:
- _id: 260AA4E2-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '747687'
name: Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells
publication: Haematologica
publication_identifier:
eissn:
- 1592-8721
issn:
- 0390-6078
publication_status: published
publisher: Ferrata Storti Foundation
quality_controlled: '1'
scopus_import: '1'
status: public
title: Single platelet and megakaryocyte morpho-dynamics uncovered by multicolor reporter
mouse strains in vitro and in vivo
tmp:
image: /images/cc_by_nc.png
legal_code_url: https://creativecommons.org/licenses/by-nc/4.0/legalcode
name: Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
short: CC BY-NC (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 107
year: '2022'
...
---
_id: '11843'
abstract:
- lang: eng
text: A key attribute of persistent or recurring bacterial infections is the ability
of the pathogen to evade the host’s immune response. Many Enterobacteriaceae express
type 1 pili, a pre-adapted virulence trait, to invade host epithelial cells and
establish persistent infections. However, the molecular mechanisms and strategies
by which bacteria actively circumvent the immune response of the host remain poorly
understood. Here, we identified CD14, the major co-receptor for lipopolysaccharide
detection, on mouse dendritic cells (DCs) as a binding partner of FimH, the protein
located at the tip of the type 1 pilus of Escherichia coli. The FimH amino acids
involved in CD14 binding are highly conserved across pathogenic and non-pathogenic
strains. Binding of the pathogenic strain CFT073 to CD14 reduced DC migration
by overactivation of integrins and blunted expression of co-stimulatory molecules
by overactivating the NFAT (nuclear factor of activated T-cells) pathway, both
rate-limiting factors of T cell activation. This response was binary at the single-cell
level, but averaged in larger populations exposed to both piliated and non-piliated
pathogens, presumably via the exchange of immunomodulatory cytokines. While defining
an active molecular mechanism of immune evasion by pathogens, the interaction
between FimH and CD14 represents a potential target to interfere with persistent
and recurrent infections, such as urinary tract infections or Crohn’s disease.
acknowledged_ssus:
- _id: Bio
- _id: PreCl
- _id: EM-Fac
acknowledgement: We thank Ulrich Dobrindt for providing UPEC strains CFT073, UTI89,
and 536, Frank Assen, Vlad Gavra, Maximilian Götz, Bor Kavčič, Jonna Alanko, and
Eva Kiermaier for help with experiments and Robert Hauschild, Julian Stopp, and
Saren Tasciyan for help with data analysis. We thank the IST Austria Scientific
Service Units, especially the Bioimaging facility, the Preclinical facility and
the Electron microscopy facility for technical support, Jakob Wallner and all members
of the Guet and Sixt lab for fruitful discussions and Daria Siekhaus for critically
reading the manuscript. This work was supported by grants from the Austrian Research
Promotion Agency (FEMtech 868984) to IG, the European Research Council (CoG 724373),
and the Austrian Science Fund (FWF P29911) to MS.
article_number: e78995
article_processing_charge: Yes
article_type: original
author:
- first_name: Kathrin
full_name: Tomasek, Kathrin
id: 3AEC8556-F248-11E8-B48F-1D18A9856A87
last_name: Tomasek
orcid: 0000-0003-3768-877X
- first_name: Alexander F
full_name: Leithner, Alexander F
id: 3B1B77E4-F248-11E8-B48F-1D18A9856A87
last_name: Leithner
orcid: 0000-0002-1073-744X
- first_name: Ivana
full_name: Glatzová, Ivana
id: 727b3c7d-4939-11ec-89b3-b9b0750ab74d
last_name: Glatzová
- first_name: Michael S.
full_name: Lukesch, Michael S.
last_name: Lukesch
- first_name: Calin C
full_name: Guet, Calin C
id: 47F8433E-F248-11E8-B48F-1D18A9856A87
last_name: Guet
orcid: 0000-0001-6220-2052
- 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: Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. Type 1 piliated
uropathogenic Escherichia coli hijack the host immune response by binding to CD14.
eLife. 2022;11. doi:10.7554/eLife.78995
apa: Tomasek, K., Leithner, A. F., Glatzová, I., Lukesch, M. S., Guet, C. C., &
Sixt, M. K. (2022). Type 1 piliated uropathogenic Escherichia coli hijack the
host immune response by binding to CD14. ELife. eLife Sciences Publications.
https://doi.org/10.7554/eLife.78995
chicago: Tomasek, Kathrin, Alexander F Leithner, Ivana Glatzová, Michael S. Lukesch,
Calin C Guet, and Michael K Sixt. “Type 1 Piliated Uropathogenic Escherichia Coli
Hijack the Host Immune Response by Binding to CD14.” ELife. eLife Sciences
Publications, 2022. https://doi.org/10.7554/eLife.78995.
ieee: K. Tomasek, A. F. Leithner, I. Glatzová, M. S. Lukesch, C. C. Guet, and M.
K. Sixt, “Type 1 piliated uropathogenic Escherichia coli hijack the host immune
response by binding to CD14,” eLife, vol. 11. eLife Sciences Publications,
2022.
ista: Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. 2022. Type
1 piliated uropathogenic Escherichia coli hijack the host immune response by binding
to CD14. eLife. 11, e78995.
mla: Tomasek, Kathrin, et al. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack
the Host Immune Response by Binding to CD14.” ELife, vol. 11, e78995, eLife
Sciences Publications, 2022, doi:10.7554/eLife.78995.
short: K. Tomasek, A.F. Leithner, I. Glatzová, M.S. Lukesch, C.C. Guet, M.K. Sixt,
ELife 11 (2022).
corr_author: '1'
date_created: 2022-08-14T22:01:46Z
date_published: 2022-07-26T00:00:00Z
date_updated: 2025-04-15T07:17:32Z
day: '26'
ddc:
- '570'
department:
- _id: MiSi
- _id: CaGu
doi: 10.7554/eLife.78995
ec_funded: 1
external_id:
isi:
- '000838410200001'
pmid:
- '35881547'
file:
- access_level: open_access
checksum: 002a3c7c7ea5caa9af9cfbea308f6ea4
content_type: application/pdf
creator: cchlebak
date_created: 2022-08-16T08:57:37Z
date_updated: 2022-08-16T08:57:37Z
file_id: '11861'
file_name: 2022_eLife_Tomasek.pdf
file_size: 2057577
relation: main_file
success: 1
file_date_updated: 2022-08-16T08:57:37Z
has_accepted_license: '1'
intvolume: ' 11'
isi: 1
language:
- iso: eng
month: '07'
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: 26018E70-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P29911
name: Mechanical adaptation of lamellipodial actin
publication: eLife
publication_identifier:
eissn:
- 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
related_material:
record:
- id: '10316'
relation: earlier_version
status: public
scopus_import: '1'
status: public
title: Type 1 piliated uropathogenic Escherichia coli hijack the host immune response
by binding to CD14
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: 11
year: '2022'
...
---
_id: '12085'
abstract:
- lang: eng
text: Molecular catch bonds are ubiquitous in biology and essential for processes
like leucocyte extravasion1 and cellular mechanosensing2. Unlike normal (slip)
bonds, catch bonds strengthen under tension. The current paradigm is that this
feature provides ‘strength on demand3’, thus enabling cells to increase rigidity
under stress1,4,5,6. However, catch bonds are often weaker than slip bonds because
they have cryptic binding sites that are usually buried7,8. Here we show that
catch bonds render reconstituted cytoskeletal actin networks stronger than slip
bonds, even though the individual bonds are weaker. Simulations show that slip
bonds remain trapped in stress-free areas, whereas weak binding allows catch bonds
to mitigate crack initiation by moving to high-tension areas. This ‘dissociation
on demand’ explains how cells combine mechanical strength with the adaptability
required for shape change, and is relevant to diseases where catch bonding is
compromised7,9, including focal segmental glomerulosclerosis10 caused by the α-actinin-4
mutant studied here. We surmise that catch bonds are the key to create life-like
materials.
acknowledgement: 'We thank M. van Hecke and C. Alkemade for critical reading of the
manuscript. We thank P. R. ten Wolde, K. Storm, W. Ellenbroek, C. Broedersz, D.
Brueckner and M. Berger for fruitful discussions. We thank W. Brieher and V. Tang
from the University of Illinois for the kind gift of purified α-actinin-4 (WT and
the K255E point mutant) and their plasmids; M. Kuit-Vinkenoog and J. den Haan for
actin and further purification of α-actinin-4; A. Goutou and I. Isturiz-Petitjean
for co-sedimentation measurements and V. Sunderlíková for the design, mutagenesis,
cloning and purifying of the α-actinin-4 constructs used in the single-molecule
experiments. We gratefully acknowledge financial support from the following sources:
research program of the Netherlands Organization for Scientific Research (NWO) (S.J.T.,
A.R. and M.J.A.); ERC Starting Grant (335672-MINICELL) (G.H.K. and Y.M.). ‘BaSyC—Building
a Synthetic Cell’ Gravitation grant (024.003.019) of the Netherlands Ministry of
Education, Culture and Science (OCW) and the Netherlands Organisation for Scientific
Research (G.H.K. and L.B.); and support from the National Institutes of Health (1R01GM126256)
(T.K. and W.J.).'
article_processing_charge: No
article_type: original
author:
- first_name: Yuval
full_name: Mulla, Yuval
last_name: Mulla
- first_name: Mario
full_name: Avellaneda Sarrió, Mario
id: DC4BA84C-56E6-11EA-AD5D-348C3DDC885E
last_name: Avellaneda Sarrió
orcid: 0000-0001-6406-524X
- first_name: Antoine
full_name: Roland, Antoine
last_name: Roland
- first_name: Lucia
full_name: Baldauf, Lucia
last_name: Baldauf
- first_name: Wonyeong
full_name: Jung, Wonyeong
last_name: Jung
- first_name: Taeyoon
full_name: Kim, Taeyoon
last_name: Kim
- first_name: Sander J.
full_name: Tans, Sander J.
last_name: Tans
- first_name: Gijsje H.
full_name: Koenderink, Gijsje H.
last_name: Koenderink
citation:
ama: Mulla Y, Avellaneda Sarrió M, Roland A, et al. Weak catch bonds make strong
networks. Nature Materials. 2022;21(9):1019-1023. doi:10.1038/s41563-022-01288-0
apa: Mulla, Y., Avellaneda Sarrió, M., Roland, A., Baldauf, L., Jung, W., Kim, T.,
… Koenderink, G. H. (2022). Weak catch bonds make strong networks. Nature Materials.
Springer Nature. https://doi.org/10.1038/s41563-022-01288-0
chicago: Mulla, Yuval, Mario Avellaneda Sarrió, Antoine Roland, Lucia Baldauf, Wonyeong
Jung, Taeyoon Kim, Sander J. Tans, and Gijsje H. Koenderink. “Weak Catch Bonds
Make Strong Networks.” Nature Materials. Springer Nature, 2022. https://doi.org/10.1038/s41563-022-01288-0.
ieee: Y. Mulla et al., “Weak catch bonds make strong networks,” Nature
Materials, vol. 21, no. 9. Springer Nature, pp. 1019–1023, 2022.
ista: Mulla Y, Avellaneda Sarrió M, Roland A, Baldauf L, Jung W, Kim T, Tans SJ,
Koenderink GH. 2022. Weak catch bonds make strong networks. Nature Materials.
21(9), 1019–1023.
mla: Mulla, Yuval, et al. “Weak Catch Bonds Make Strong Networks.” Nature Materials,
vol. 21, no. 9, Springer Nature, 2022, pp. 1019–23, doi:10.1038/s41563-022-01288-0.
short: Y. Mulla, M. Avellaneda Sarrió, A. Roland, L. Baldauf, W. Jung, T. Kim, S.J.
Tans, G.H. Koenderink, Nature Materials 21 (2022) 1019–1023.
date_created: 2022-09-11T22:01:57Z
date_published: 2022-09-01T00:00:00Z
date_updated: 2023-08-03T14:08:47Z
day: '01'
department:
- _id: MiSi
doi: 10.1038/s41563-022-01288-0
external_id:
isi:
- '000844592000002'
pmid:
- '36008604'
intvolume: ' 21'
isi: 1
issue: '9'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1101/2020.07.27.219618
month: '09'
oa: 1
oa_version: Preprint
page: 1019-1023
pmid: 1
publication: Nature Materials
publication_identifier:
eissn:
- 1476-4660
issn:
- 1476-1122
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Weak catch bonds make strong networks
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 21
year: '2022'
...
---
_id: '12119'
abstract:
- lang: eng
text: Intravascular neutrophils and platelets collaborate in maintaining host integrity,
but their interaction can also trigger thrombotic complications. We report here
that cooperation between neutrophil and platelet lineages extends to the earliest
stages of platelet formation by megakaryocytes in the bone marrow. Using intravital
microscopy, we show that neutrophils “plucked” intravascular megakaryocyte extensions,
termed proplatelets, to control platelet production. Following CXCR4-CXCL12-dependent
migration towards perisinusoidal megakaryocytes, plucking neutrophils actively
pulled on proplatelets and triggered myosin light chain and extracellular-signal-regulated
kinase activation through reactive oxygen species. By these mechanisms, neutrophils
accelerate proplatelet growth and facilitate continuous release of platelets in
steady state. Following myocardial infarction, plucking neutrophils drove excessive
release of young, reticulated platelets and boosted the risk of recurrent ischemia.
Ablation of neutrophil plucking normalized thrombopoiesis and reduced recurrent
thrombosis after myocardial infarction and thrombus burden in venous thrombosis.
We establish neutrophil plucking as a target to reduce thromboischemic events.
acknowledgement: "We thank Coung Kieu and Dominik van den Heuvel for excellent technical
assistance. This work was supported by the German Research Foundation (PE2704/2-1,
PE2704/3-1 to T.P., SFB 1123-project B06 to S.M., SFB1525 project A07 to D.S, TRR
332 project A7 to C.S., PO 2247/2-1 to A.P., SFB1116-project B11 to A.P. and B12
to M.K.), LMU Munich’s Institutional\r\nStrategy LMUexcellent within the framework
of the German Excellence Initiative (No. 806 32 006 to T.P.), and by the German
Centre for Cardiovascular Research (DZHK) to T.P. (Postdoc Start-up grant No. 100378833).
This project has received funding from the European Research Council (ERC) under
the European Union’s Horizon 2020 research and innovation program (grant agreement
No. 833440 to S.M.). F.G. received funding from the European Union’s\r\nHorizon
2020 research and innovation program under the Marie Sk1odowska-Curie grant agreement
no. 747687. A.H. was funded by RTI2018-095497-B-I00 from Ministerio de Ciencia e
Innovacio´ n (MICINN), HR17_00527 from Fundacion La Caixa, and Transatlantic Network
of Excellence (TNE-18CVD04) from the Leducq Foundation. The CNIC is supported by
the MICINN and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence
(CEX2020-001041-S). A.P. was supported by the Forschungskommission of the Medical
Faculty of the Heinrich-Heine-Universität Düsseldorf (No. 18-2019 to A.P.). C.G.
was supported by the Helmholtz Alliance ‘Aging and Metabolic Programming, AMPro,’
by the German Federal\r\nMinistry of Education and Research to the German Center
for Diabetes Research (DZD), and by the Bavarian State Ministry of Health and Care
through the research project DigiMed Bayern."
article_processing_charge: No
article_type: original
author:
- first_name: Tobias
full_name: Petzold, Tobias
last_name: Petzold
- first_name: Zhe
full_name: Zhang, Zhe
last_name: Zhang
- first_name: Iván
full_name: Ballesteros, Iván
last_name: Ballesteros
- first_name: Inas
full_name: Saleh, Inas
last_name: Saleh
- first_name: Amin
full_name: Polzin, Amin
last_name: Polzin
- first_name: Manuela
full_name: Thienel, Manuela
last_name: Thienel
- first_name: Lulu
full_name: Liu, Lulu
last_name: Liu
- first_name: Qurrat
full_name: Ul Ain, Qurrat
last_name: Ul Ain
- first_name: Vincent
full_name: Ehreiser, Vincent
last_name: Ehreiser
- first_name: Christian
full_name: Weber, Christian
last_name: Weber
- first_name: Badr
full_name: Kilani, Badr
last_name: Kilani
- first_name: Pontus
full_name: Mertsch, Pontus
last_name: Mertsch
- first_name: Jeremias
full_name: Götschke, Jeremias
last_name: Götschke
- first_name: Sophie
full_name: Cremer, Sophie
last_name: Cremer
- first_name: Wenwen
full_name: Fu, Wenwen
last_name: Fu
- first_name: Michael
full_name: Lorenz, Michael
last_name: Lorenz
- first_name: Hellen
full_name: Ishikawa-Ankerhold, Hellen
last_name: Ishikawa-Ankerhold
- first_name: Elisabeth
full_name: Raatz, Elisabeth
last_name: Raatz
- first_name: Shaza
full_name: El-Nemr, Shaza
last_name: El-Nemr
- first_name: Agnes
full_name: Görlach, Agnes
last_name: Görlach
- first_name: Esther
full_name: Marhuenda, Esther
last_name: Marhuenda
- first_name: Konstantin
full_name: Stark, Konstantin
last_name: Stark
- first_name: Joachim
full_name: Pircher, Joachim
last_name: Pircher
- first_name: David
full_name: Stegner, David
last_name: Stegner
- first_name: Christian
full_name: Gieger, Christian
last_name: Gieger
- first_name: Marc
full_name: Schmidt-Supprian, Marc
last_name: Schmidt-Supprian
- first_name: Florian R
full_name: Gärtner, Florian R
id: 397A88EE-F248-11E8-B48F-1D18A9856A87
last_name: Gärtner
orcid: 0000-0001-6120-3723
- first_name: Isaac
full_name: Almendros, Isaac
last_name: Almendros
- first_name: Malte
full_name: Kelm, Malte
last_name: Kelm
- first_name: Christian
full_name: Schulz, Christian
last_name: Schulz
- first_name: Andrés
full_name: Hidalgo, Andrés
last_name: Hidalgo
- first_name: Steffen
full_name: Massberg, Steffen
last_name: Massberg
citation:
ama: Petzold T, Zhang Z, Ballesteros I, et al. Neutrophil “plucking” on megakaryocytes
drives platelet production and boosts cardiovascular disease. Immunity.
2022;55(12):2285-2299.e7. doi:10.1016/j.immuni.2022.10.001
apa: Petzold, T., Zhang, Z., Ballesteros, I., Saleh, I., Polzin, A., Thienel, M.,
… Massberg, S. (2022). Neutrophil “plucking” on megakaryocytes drives platelet
production and boosts cardiovascular disease. Immunity. Elsevier. https://doi.org/10.1016/j.immuni.2022.10.001
chicago: Petzold, Tobias, Zhe Zhang, Iván Ballesteros, Inas Saleh, Amin Polzin,
Manuela Thienel, Lulu Liu, et al. “Neutrophil ‘Plucking’ on Megakaryocytes Drives
Platelet Production and Boosts Cardiovascular Disease.” Immunity. Elsevier,
2022. https://doi.org/10.1016/j.immuni.2022.10.001.
ieee: T. Petzold et al., “Neutrophil ‘plucking’ on megakaryocytes drives
platelet production and boosts cardiovascular disease,” Immunity, vol.
55, no. 12. Elsevier, p. 2285–2299.e7, 2022.
ista: Petzold T, Zhang Z, Ballesteros I, Saleh I, Polzin A, Thienel M, Liu L, Ul
Ain Q, Ehreiser V, Weber C, Kilani B, Mertsch P, Götschke J, Cremer S, Fu W, Lorenz
M, Ishikawa-Ankerhold H, Raatz E, El-Nemr S, Görlach A, Marhuenda E, Stark K,
Pircher J, Stegner D, Gieger C, Schmidt-Supprian M, Gärtner FR, Almendros I, Kelm
M, Schulz C, Hidalgo A, Massberg S. 2022. Neutrophil “plucking” on megakaryocytes
drives platelet production and boosts cardiovascular disease. Immunity. 55(12),
2285–2299.e7.
mla: Petzold, Tobias, et al. “Neutrophil ‘Plucking’ on Megakaryocytes Drives Platelet
Production and Boosts Cardiovascular Disease.” Immunity, vol. 55, no. 12,
Elsevier, 2022, p. 2285–2299.e7, doi:10.1016/j.immuni.2022.10.001.
short: T. Petzold, Z. Zhang, I. Ballesteros, I. Saleh, A. Polzin, M. Thienel, L.
Liu, Q. Ul Ain, V. Ehreiser, C. Weber, B. Kilani, P. Mertsch, J. Götschke, S.
Cremer, W. Fu, M. Lorenz, H. Ishikawa-Ankerhold, E. Raatz, S. El-Nemr, A. Görlach,
E. Marhuenda, K. Stark, J. Pircher, D. Stegner, C. Gieger, M. Schmidt-Supprian,
F.R. Gärtner, I. Almendros, M. Kelm, C. Schulz, A. Hidalgo, S. Massberg, Immunity
55 (2022) 2285–2299.e7.
date_created: 2023-01-12T11:56:54Z
date_published: 2022-12-13T00:00:00Z
date_updated: 2025-04-14T07:43:16Z
day: '13'
ddc:
- '570'
department:
- _id: MiSi
doi: 10.1016/j.immuni.2022.10.001
ec_funded: 1
external_id:
isi:
- '000922019600003'
pmid:
- '36272416'
file:
- access_level: open_access
checksum: 073267a9c0ad9f85a650053bc7b23777
content_type: application/pdf
creator: dernst
date_created: 2023-01-23T10:18:48Z
date_updated: 2023-01-23T10:18:48Z
file_id: '12341'
file_name: 2022_Immunity_Petzold.pdf
file_size: 5299475
relation: main_file
success: 1
file_date_updated: 2023-01-23T10:18:48Z
has_accepted_license: '1'
intvolume: ' 55'
isi: 1
issue: '12'
keyword:
- Infectious Diseases
- Immunology
- Immunology and Allergy
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc-nd/4.0/
month: '12'
oa: 1
oa_version: Published Version
page: 2285-2299.e7
pmid: 1
project:
- _id: 260AA4E2-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '747687'
name: Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells
publication: Immunity
publication_identifier:
issn:
- 1074-7613
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Neutrophil “plucking” on megakaryocytes drives platelet production and boosts
cardiovascular disease
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: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 55
year: '2022'
...
---
_id: '12133'
abstract:
- lang: eng
text: Social distancing is an effective way to prevent the spread of disease in
societies, whereas infection elimination is a key element of organismal immunity.
Here, we discuss how the study of social insects such as ants — which form a superorganism
of unconditionally cooperative individuals and thus represent a level of organization
that is intermediate between a classical society of individuals and an organism
of cells — can help to determine common principles of disease defence across levels
of organization.
article_processing_charge: No
article_type: letter_note
author:
- first_name: Sylvia
full_name: Cremer, Sylvia
id: 2F64EC8C-F248-11E8-B48F-1D18A9856A87
last_name: Cremer
orcid: 0000-0002-2193-3868
- 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: Cremer S, Sixt MK. Principles of disease defence in organisms, superorganisms
and societies. Nature Reviews Immunology. 2022;22(12):713-714. doi:10.1038/s41577-022-00797-y
apa: Cremer, S., & Sixt, M. K. (2022). Principles of disease defence in organisms,
superorganisms and societies. Nature Reviews Immunology. Springer Nature.
https://doi.org/10.1038/s41577-022-00797-y
chicago: Cremer, Sylvia, and Michael K Sixt. “Principles of Disease Defence in Organisms,
Superorganisms and Societies.” Nature Reviews Immunology. Springer Nature,
2022. https://doi.org/10.1038/s41577-022-00797-y.
ieee: S. Cremer and M. K. Sixt, “Principles of disease defence in organisms, superorganisms
and societies,” Nature Reviews Immunology, vol. 22, no. 12. Springer Nature,
pp. 713–714, 2022.
ista: Cremer S, Sixt MK. 2022. Principles of disease defence in organisms, superorganisms
and societies. Nature Reviews Immunology. 22(12), 713–714.
mla: Cremer, Sylvia, and Michael K. Sixt. “Principles of Disease Defence in Organisms,
Superorganisms and Societies.” Nature Reviews Immunology, vol. 22, no.
12, Springer Nature, 2022, pp. 713–14, doi:10.1038/s41577-022-00797-y.
short: S. Cremer, M.K. Sixt, Nature Reviews Immunology 22 (2022) 713–714.
corr_author: '1'
date_created: 2023-01-12T12:03:14Z
date_published: 2022-12-01T00:00:00Z
date_updated: 2024-10-09T21:03:33Z
day: '01'
department:
- _id: SyCr
- _id: MiSi
doi: 10.1038/s41577-022-00797-y
external_id:
isi:
- '000871836300001'
pmid:
- '36284178'
intvolume: ' 22'
isi: 1
issue: '12'
keyword:
- Energy Engineering and Power Technology
- Fuel Technology
language:
- iso: eng
month: '12'
oa_version: None
page: 713-714
pmid: 1
publication: Nature Reviews Immunology
publication_identifier:
eissn:
- 1474-1741
issn:
- 1474-1733
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Principles of disease defence in organisms, superorganisms and societies
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 22
year: '2022'
...
---
_id: '17072'
abstract:
- lang: eng
text: The collapse of polypeptides is thought important to protein folding, aggregation,
intrinsic disorder, and phase separation. However, whether polypeptide collapse
is modulated in cells to control protein states is unclear. Here, using integrated
protein manipulation and imaging, we show that the chaperonin GroEL-ES can accelerate
the folding of proteins by strengthening their collapse. GroEL induces contractile
forces in substrate chains, which draws them into the cavity and triggers a general
compaction and discrete folding transitions, even for slow-folding proteins. This
collapse enhancement is strongest in the nucleotide-bound states of GroEL and
is aided by GroES binding to the cavity rim and by the amphiphilic C-terminal
tails at the cavity bottom. Collapse modulation is distinct from other proposed
GroEL-ES folding acceleration mechanisms, including steric confinement and misfold
unfolding. Given the prevalence of collapse throughout the proteome, we conjecture
that collapse modulation is more generally relevant within the protein quality
control machinery.
acknowledgement: We thank A. L. Horwich, K. Chakraborty, and B. Schuler for providing
plasmids, and R. van Leeuwen, M. Mayer, J. van Zon, W. Noorduin, and P. R. ten Wolde
for comments and critical reading of the manuscript. Work in the group of S.J.T.
was supported by the Netherlands Organization for Scientific Research (NWO). Work
in the group of H.S.R. was supported by a grant from the NIH (R01GM114405).
article_number: eabl6293
article_processing_charge: Yes
article_type: original
author:
- first_name: Mohsin M.
full_name: Naqvi, Mohsin M.
last_name: Naqvi
- first_name: Mario
full_name: Avellaneda Sarrió, Mario
id: DC4BA84C-56E6-11EA-AD5D-348C3DDC885E
last_name: Avellaneda Sarrió
orcid: 0000-0001-6406-524X
- first_name: Andrew
full_name: Roth, Andrew
last_name: Roth
- first_name: Eline J.
full_name: Koers, Eline J.
last_name: Koers
- first_name: Antoine
full_name: Roland, Antoine
last_name: Roland
- first_name: Vanda
full_name: Sunderlikova, Vanda
last_name: Sunderlikova
- first_name: Günter
full_name: Kramer, Günter
last_name: Kramer
- first_name: Hays S.
full_name: Rye, Hays S.
last_name: Rye
- first_name: Sander J.
full_name: Tans, Sander J.
last_name: Tans
citation:
ama: Naqvi MM, Avellaneda Sarrió M, Roth A, et al. Protein chain collapse modulation
and folding stimulation by GroEL-ES. Science Advances. 2022;8(9). doi:10.1126/sciadv.abl6293
apa: Naqvi, M. M., Avellaneda Sarrió, M., Roth, A., Koers, E. J., Roland, A., Sunderlikova,
V., … Tans, S. J. (2022). Protein chain collapse modulation and folding stimulation
by GroEL-ES. Science Advances. American Association for the Advancement
of Science. https://doi.org/10.1126/sciadv.abl6293
chicago: Naqvi, Mohsin M., Mario Avellaneda Sarrió, Andrew Roth, Eline J. Koers,
Antoine Roland, Vanda Sunderlikova, Günter Kramer, Hays S. Rye, and Sander J.
Tans. “Protein Chain Collapse Modulation and Folding Stimulation by GroEL-ES.”
Science Advances. American Association for the Advancement of Science,
2022. https://doi.org/10.1126/sciadv.abl6293.
ieee: M. M. Naqvi et al., “Protein chain collapse modulation and folding
stimulation by GroEL-ES,” Science Advances, vol. 8, no. 9. American Association
for the Advancement of Science, 2022.
ista: Naqvi MM, Avellaneda Sarrió M, Roth A, Koers EJ, Roland A, Sunderlikova V,
Kramer G, Rye HS, Tans SJ. 2022. Protein chain collapse modulation and folding
stimulation by GroEL-ES. Science Advances. 8(9), eabl6293.
mla: Naqvi, Mohsin M., et al. “Protein Chain Collapse Modulation and Folding Stimulation
by GroEL-ES.” Science Advances, vol. 8, no. 9, eabl6293, American Association
for the Advancement of Science, 2022, doi:10.1126/sciadv.abl6293.
short: M.M. Naqvi, M. Avellaneda Sarrió, A. Roth, E.J. Koers, A. Roland, V. Sunderlikova,
G. Kramer, H.S. Rye, S.J. Tans, Science Advances 8 (2022).
date_created: 2024-05-29T06:12:19Z
date_published: 2022-03-01T00:00:00Z
date_updated: 2024-08-05T08:30:29Z
day: '01'
ddc:
- '570'
department:
- _id: MiSi
doi: 10.1126/sciadv.abl6293
external_id:
pmid:
- '35245117'
file:
- access_level: open_access
checksum: 9511579306cce7e04107d3d6389ed614
content_type: application/pdf
creator: dernst
date_created: 2024-07-31T12:01:51Z
date_updated: 2024-07-31T12:01:51Z
file_id: '17357'
file_name: 2022_ScienceAdv_Naqvi.pdf
file_size: 2404150
relation: main_file
success: 1
file_date_updated: 2024-07-31T12:01:51Z
has_accepted_license: '1'
intvolume: ' 8'
issue: '9'
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
pmid: 1
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: Protein chain collapse modulation and folding stimulation by GroEL-ES
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: 8
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. Nature Immunology. 2022;23:1246-1255. doi:10.1038/s41590-022-01257-4
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. Nature Immunology. Springer Nature. https://doi.org/10.1038/s41590-022-01257-4
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.” Nature Immunology. Springer Nature,
2022. https://doi.org/10.1038/s41590-022-01257-4.
ieee: F. P. Assen et al., “Multitier mechanics control stromal adaptations
in swelling lymph nodes,” Nature Immunology, 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.” Nature Immunology, vol. 23, Springer Nature, 2022,
pp. 1246–55, doi:10.1038/s41590-022-01257-4.
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'
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call_identifier: H2020
grant_number: '724373'
name: Cellular Navigation Along Spatial Gradients
publication: Nature Immunology
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title: Multitier mechanics control stromal adaptations in swelling lymph nodes
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