---
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
PlanS_conform: '1'
_id: '22963'
abstract:
- lang: eng
  text: Although studies of tumor invasion have mainly emphasized the evolution of
    genetic and epigenetic heterogeneity, cellular behaviors also depend on the physical
    microenvironment. Yet, the tumor microenvironment is both complex and continuously
    remodeled, making it hard to rigorously test its causal influence on tumor dissemination.
    Here, we adopted a reductionist approach to studying tumor cell invasion in microengineered
    environments of tunable patterned geometries. We find that not only the presence
    of obstacles but more unexpectedly their spatial disorder causes a drastic shift
    from a collective to a single-cell mode of invasion—comparable in strength to
    loss of cell-cell adhesion. Combining live-imaging and perturbation experiments
    with minimal biophysical modeling, we demonstrate that cell dissemination results
    both from local geometrical constraints and a global integration of spatial disorder
    over time. We identify generic universality classes of invasion dynamics dependent
    on environmental geometry, enabling us to identify quantitative physical principles
    for tumor dissemination.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
acknowledgement: 'We thank all the members of the Hannezo and Sixt groups for fruitful
  discussions and t. Kato for advice on the experimental setup. We are also thankful
  for support from the Scientific Service Units (SSU) of IST Austria through resources
  provided by the imaging and Optics Facility (iOF) and the Lab Support Facility (lSF).
  We used chatGPt (GPt- 5,OpenAi, 2025) to make minor grammatical and stylistic revisions
  to the original manuscript, which was written by us. We carefully reviewed and verified
  all changes and are solely responsible for all scientific content, data, interpretation,
  and conclusions. Funding: Z.D. has received funding from the Doctoral Programme
  of the Austrian Academy of Sciences (OeAW):grant agreement 26360. this work was
  supported by the European Research council (grant ERC- SyG 101071793 to M.S.). E.S.
  and R.P.J. are supported by the Francis Crick Institute, which receives its core
  funding from cancer Research UK (cc2040), the UK Medical Research council(cc2040),
  and the Wellcome trust (cc2040) and the European Research council (ERC Advanced
  Grant cAn_ORGAniSe, grant agreement number 101019366).'
article_number: eaed0587
article_processing_charge: Yes
article_type: original
author:
- first_name: Zuzana
  full_name: Dunajova, Zuzana
  id: 4B39F286-F248-11E8-B48F-1D18A9856A87
  last_name: Dunajova
- first_name: Saren
  full_name: Tasciyan, Saren
  id: 4323B49C-F248-11E8-B48F-1D18A9856A87
  last_name: Tasciyan
  orcid: 0000-0003-1671-393X
- first_name: Juraj
  full_name: Majek, Juraj
  id: 3e6d9473-f38e-11ec-8ae0-c4e05a8aa9e1
  last_name: Majek
- first_name: Jack
  full_name: Merrin, Jack
  id: 4515C308-F248-11E8-B48F-1D18A9856A87
  last_name: Merrin
  orcid: 0000-0001-5145-4609
- first_name: Robert P.
  full_name: Jenkins, Robert P.
  last_name: Jenkins
- first_name: Erik
  full_name: Sahai, Erik
  last_name: Sahai
- 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: Edouard B
  full_name: Hannezo, Edouard B
  id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
  last_name: Hannezo
  orcid: 0000-0001-6005-1561
citation:
  ama: Dunajova Z, Tasciyan S, Majek J, et al. Substrate heterogeneity promotes cancer
    cell dissemination through interface roughening. <i>Science Advances</i>. 2026;12(37).
    doi:<a href="https://doi.org/10.1126/sciadv.aed0587">10.1126/sciadv.aed0587</a>
  apa: Dunajova, Z., Tasciyan, S., Majek, J., Merrin, J., Jenkins, R. P., Sahai, E.,
    … Hannezo, E. B. (2026). Substrate heterogeneity promotes cancer cell dissemination
    through interface roughening. <i>Science Advances</i>. AAAS. <a href="https://doi.org/10.1126/sciadv.aed0587">https://doi.org/10.1126/sciadv.aed0587</a>
  chicago: Dunajova, Zuzana, Saren Tasciyan, Juraj Majek, Jack Merrin, Robert P. Jenkins,
    Erik Sahai, Michael K Sixt, and Edouard B Hannezo. “Substrate Heterogeneity Promotes
    Cancer Cell Dissemination through Interface Roughening.” <i>Science Advances</i>.
    AAAS, 2026. <a href="https://doi.org/10.1126/sciadv.aed0587">https://doi.org/10.1126/sciadv.aed0587</a>.
  ieee: Z. Dunajova <i>et al.</i>, “Substrate heterogeneity promotes cancer cell dissemination
    through interface roughening,” <i>Science Advances</i>, vol. 12, no. 37. AAAS,
    2026.
  ista: Dunajova Z, Tasciyan S, Majek J, Merrin J, Jenkins RP, Sahai E, Sixt MK, Hannezo
    EB. 2026. Substrate heterogeneity promotes cancer cell dissemination through interface
    roughening. Science Advances. 12(37), eaed0587.
  mla: Dunajova, Zuzana, et al. “Substrate Heterogeneity Promotes Cancer Cell Dissemination
    through Interface Roughening.” <i>Science Advances</i>, vol. 12, no. 37, eaed0587,
    AAAS, 2026, doi:<a href="https://doi.org/10.1126/sciadv.aed0587">10.1126/sciadv.aed0587</a>.
  short: Z. Dunajova, S. Tasciyan, J. Majek, J. Merrin, R.P. Jenkins, E. Sahai, M.K.
    Sixt, E.B. Hannezo, Science Advances 12 (2026).
corr_author: '1'
das_tickbox: '1'
dataavailabilitystatement: ' All data and code needed to evaluate and reproduce the
  results in the paper are present in the paper and/or the Supplementary Materials
  and the associated data and code repositories. Source data underlying all figures
  and supplementary figures have been deposited in a Zenodo repository (DOi: 10.5281/zenodo.21718217)
  and will be made publicly available upon publication. custom simulation and analysis
  codes used in this study are available at https://codeocean.com/capsule/1237446/tree.
  no unique biological materials were generated in this study. Microfluidic mask designs
  generated for this work are available from the corresponding authors upon reasonable
  request.'
date_created: 2026-09-20T22:01:48Z
date_published: 2026-09-09T00:00:00Z
date_updated: 2026-10-06T11:36:34Z
day: '09'
ddc:
- '570'
department:
- _id: EdHa
- _id: MiSi
- _id: GradSch
- _id: AnSa
- _id: NanoFab
doi: 10.1126/sciadv.aed0587
external_id:
  pmid:
  - '42715298'
file:
- access_level: open_access
  checksum: 79f419b659650a39b3dfa58c782690a8
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  creator: dernst
  date_created: 2026-10-06T11:30:48Z
  date_updated: 2026-10-06T11:30:48Z
  file_id: '23062'
  file_name: 2026_ScienceAdv_Dunajova.pdf
  file_size: 11691064
  relation: main_file
  success: 1
file_date_updated: 2026-10-06T11:30:48Z
fulldoi: https://doi.org/10.1126/sciadv.aed0587
has_accepted_license: '1'
intvolume: '        12'
issue: '37'
language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
month: '09'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 34d75525-11ca-11ed-8bc3-89b6307fee9d
  grant_number: '26360'
  name: Motile active matter models of migrating cells and chiral filaments
- _id: bd91e723-d553-11ed-ba76-fe7eeb2185fd
  grant_number: '101071793'
  name: 'Pushing from within: Control of cell shape, integrity and motility by cytoskeletal
    pushing forces'
publication: Science Advances
publication_identifier:
  eissn:
  - 2375-2548
publication_status: published
publisher: AAAS
quality_controlled: '1'
related_material:
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researchdata_availability: yes
scopus_import: '1'
status: public
supplementarymaterial: no
title: Substrate heterogeneity promotes cancer cell dissemination through interface
  roughening
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: 12
year: '2026'
...
---
OA_place: repository
_id: '21427'
abstract:
- lang: eng
  text: While tumor malignancy has been extensively studied under the prism of genetic
    and epigenetic heterogeneity, tumor cell states also critically depend on reciprocal
    interactions with the microenvironment. This raises the hitherto untested possibility
    that heterogeneity of the untransformed tumor stroma can actively fuel malignant
    progression. As biological heterogeneity is inherently difficult to control, we
    adopted a reductionist approach and let tumor cells invade micro-engineered environments
    harboring obstacles with precision-controlled geometry. We find that not only
    the presence of obstacles, but more surprisingly their spatial disorder, causes
    a drastic shift from a collective to a single-cell mode of invasion – comparable
    in strength to cadherin loss. Combining live-imaging and perturbation experiments
    with minimal biophysical modeling, we demonstrate that cell detachments result
    both from local geometrical constraints and a global integration of spatial disorder
    over time. We show that different types of microenvironments map onto different
    universality classes of invasion dynamics - homogeneous substrates follow Kardar–Parisi–Zhang
    (KPZ) scaling, while disordered ones exhibit exponents consistent with KPZ with
    quenched disorder (KPZq). Our findings highlight generic physical principles for
    how the mode of cancer cell invasion depends on environmental heterogeneity, with
    potential implications to understand tumor evolution in vivo.
acknowledgement: "European Research Council, https://ror.org/0472cxd90, 101071793\r\nAustrian
  Academy of Sciences, 26360"
article_processing_charge: No
author:
- first_name: Zuzana
  full_name: Dunajova, Zuzana
  id: 4B39F286-F248-11E8-B48F-1D18A9856A87
  last_name: Dunajova
- first_name: Saren
  full_name: Tasciyan, Saren
  id: 4323B49C-F248-11E8-B48F-1D18A9856A87
  last_name: Tasciyan
  orcid: 0000-0003-1671-393X
- first_name: Juraj
  full_name: Majek, Juraj
  id: 3e6d9473-f38e-11ec-8ae0-c4e05a8aa9e1
  last_name: Majek
- first_name: Jack
  full_name: Merrin, Jack
  id: 4515C308-F248-11E8-B48F-1D18A9856A87
  last_name: Merrin
  orcid: 0000-0001-5145-4609
- first_name: Erik
  full_name: Sahai, Erik
  last_name: Sahai
- 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: Edouard B
  full_name: Hannezo, Edouard B
  id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
  last_name: Hannezo
  orcid: 0000-0001-6005-1561
citation:
  ama: Dunajova Z, Tasciyan S, Majek J, et al. Substrate heterogeneity promotes cancer
    cell dissemination through interface roughening. <i>bioRxiv</i>. doi:<a href="https://doi.org/10.1101/2025.05.20.655037">10.1101/2025.05.20.655037</a>
  apa: Dunajova, Z., Tasciyan, S., Majek, J., Merrin, J., Sahai, E., Sixt, M. K.,
    &#38; Hannezo, E. B. (n.d.). Substrate heterogeneity promotes cancer cell dissemination
    through interface roughening. <i>bioRxiv</i>. <a href="https://doi.org/10.1101/2025.05.20.655037">https://doi.org/10.1101/2025.05.20.655037</a>
  chicago: Dunajova, Zuzana, Saren Tasciyan, Juraj Majek, Jack Merrin, Erik Sahai,
    Michael K Sixt, and Edouard B Hannezo. “Substrate Heterogeneity Promotes Cancer
    Cell Dissemination through Interface Roughening.” <i>BioRxiv</i>, n.d. <a href="https://doi.org/10.1101/2025.05.20.655037">https://doi.org/10.1101/2025.05.20.655037</a>.
  ieee: Z. Dunajova <i>et al.</i>, “Substrate heterogeneity promotes cancer cell dissemination
    through interface roughening,” <i>bioRxiv</i>. .
  ista: Dunajova Z, Tasciyan S, Majek J, Merrin J, Sahai E, Sixt MK, Hannezo EB. Substrate
    heterogeneity promotes cancer cell dissemination through interface roughening.
    bioRxiv, <a href="https://doi.org/10.1101/2025.05.20.655037">10.1101/2025.05.20.655037</a>.
  mla: Dunajova, Zuzana, et al. “Substrate Heterogeneity Promotes Cancer Cell Dissemination
    through Interface Roughening.” <i>BioRxiv</i>, doi:<a href="https://doi.org/10.1101/2025.05.20.655037">10.1101/2025.05.20.655037</a>.
  short: Z. Dunajova, S. Tasciyan, J. Majek, J. Merrin, E. Sahai, M.K. Sixt, E.B.
    Hannezo, BioRxiv (n.d.).
corr_author: '1'
das_tickbox: '1'
date_created: 2026-03-11T08:40:06Z
date_published: 2025-09-25T00:00:00Z
date_updated: 2026-10-29T23:31:07Z
day: '25'
ddc:
- '539'
- '570'
department:
- _id: GradSch
- _id: EdHa
- _id: MiSi
- _id: NanoFab
- _id: AnSa
doi: 10.1101/2025.05.20.655037
fulldoi: https://doi.org/10.1101/2025.05.20.655037
has_accepted_license: '1'
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc-nd/4.0/
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1101/2025.05.20.655037
month: '09'
oa: 1
oa_version: Preprint
project:
- _id: bd91e723-d553-11ed-ba76-fe7eeb2185fd
  grant_number: '101071793'
  name: 'Pushing from within: Control of cell shape, integrity and motility by cytoskeletal
    pushing forces'
- _id: 34d75525-11ca-11ed-8bc3-89b6307fee9d
  grant_number: '26360'
  name: Motile active matter models of migrating cells and chiral filaments
publication: bioRxiv
publication_status: draft
related_material:
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  - id: '21423'
    relation: dissertation_contains
    status: public
status: public
title: Substrate heterogeneity promotes cancer cell dissemination through interface
  roughening
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: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2025'
...
---
_id: '14844'
abstract:
- lang: eng
  text: 'Many cell functions require a concerted effort from multiple membrane proteins,
    for example, for signaling, cell division, and endocytosis. One contribution to
    their successful self-organization stems from the membrane deformations that these
    proteins induce. While the pairwise interaction potential of two membrane-deforming
    spheres has recently been measured, membrane-deformation-induced interactions
    have been predicted to be nonadditive, and hence their collective behavior cannot
    be deduced from this measurement. We here employ a colloidal model system consisting
    of adhesive spheres and giant unilamellar vesicles to test these predictions by
    measuring the interaction potential of the simplest case of three membrane-deforming,
    spherical particles. We quantify their interactions and arrangements and, for
    the first time, experimentally confirm and quantify the nonadditive nature of
    membrane-deformation-induced interactions. We furthermore conclude that there
    exist two favorable configurations on the membrane: (1) a linear and (2) a triangular
    arrangement of the three spheres. Using Monte Carlo simulations, we corroborate
    the experimentally observed energy minima and identify a lowering of the membrane
    deformation as the cause for the observed configurations. The high symmetry of
    the preferred arrangements for three particles suggests that arrangements of many
    membrane-deforming objects might follow simple rules.'
acknowledgement: We gratefully acknowledge useful discussions with Casper van der
  Wel, help by Yogesh Shelke with PAA coverslip preparation, and support by Rachel
  Doherty with particle functionalization. A.A. and D.J.K. would like to thank Timon
  Idema and George Dadunashvili for initial attempts to simulate the experimental
  system. D.J.K. would like to thank the physics department at Leiden University for
  funding the PhD position of A.A. B.M. and A.Š. acknowledge funding by the European
  Union’s Horizon 2020 research and innovation programme (ERC starting grant no. 802960).
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Ali
  full_name: Azadbakht, Ali
  last_name: Azadbakht
- first_name: Billie
  full_name: Meadowcroft, Billie
  id: a4725fd6-932b-11ed-81e2-c098c7f37ae1
  last_name: Meadowcroft
  orcid: 0000-0003-3441-1337
- first_name: Juraj
  full_name: Majek, Juraj
  id: 3e6d9473-f38e-11ec-8ae0-c4e05a8aa9e1
  last_name: Majek
- first_name: Anđela
  full_name: Šarić, Anđela
  id: bf63d406-f056-11eb-b41d-f263a6566d8b
  last_name: Šarić
  orcid: 0000-0002-7854-2139
- first_name: Daniela J.
  full_name: Kraft, Daniela J.
  last_name: Kraft
citation:
  ama: Azadbakht A, Meadowcroft B, Majek J, Šarić A, Kraft DJ. Nonadditivity in interactions
    between three membrane-wrapped colloidal spheres. <i>Biophysical Journal</i>.
    2024;123(3):307-316. doi:<a href="https://doi.org/10.1016/j.bpj.2023.12.020">10.1016/j.bpj.2023.12.020</a>
  apa: Azadbakht, A., Meadowcroft, B., Majek, J., Šarić, A., &#38; Kraft, D. J. (2024).
    Nonadditivity in interactions between three membrane-wrapped colloidal spheres.
    <i>Biophysical Journal</i>. Elsevier. <a href="https://doi.org/10.1016/j.bpj.2023.12.020">https://doi.org/10.1016/j.bpj.2023.12.020</a>
  chicago: Azadbakht, Ali, Billie Meadowcroft, Juraj Majek, Anđela Šarić, and Daniela
    J. Kraft. “Nonadditivity in Interactions between Three Membrane-Wrapped Colloidal
    Spheres.” <i>Biophysical Journal</i>. Elsevier, 2024. <a href="https://doi.org/10.1016/j.bpj.2023.12.020">https://doi.org/10.1016/j.bpj.2023.12.020</a>.
  ieee: A. Azadbakht, B. Meadowcroft, J. Majek, A. Šarić, and D. J. Kraft, “Nonadditivity
    in interactions between three membrane-wrapped colloidal spheres,” <i>Biophysical
    Journal</i>, vol. 123, no. 3. Elsevier, pp. 307–316, 2024.
  ista: Azadbakht A, Meadowcroft B, Majek J, Šarić A, Kraft DJ. 2024. Nonadditivity
    in interactions between three membrane-wrapped colloidal spheres. Biophysical
    Journal. 123(3), 307–316.
  mla: Azadbakht, Ali, et al. “Nonadditivity in Interactions between Three Membrane-Wrapped
    Colloidal Spheres.” <i>Biophysical Journal</i>, vol. 123, no. 3, Elsevier, 2024,
    pp. 307–16, doi:<a href="https://doi.org/10.1016/j.bpj.2023.12.020">10.1016/j.bpj.2023.12.020</a>.
  short: A. Azadbakht, B. Meadowcroft, J. Majek, A. Šarić, D.J. Kraft, Biophysical
    Journal 123 (2024) 307–316.
das_tickbox: '0'
date_created: 2024-01-21T23:00:56Z
date_published: 2024-02-06T00:00:00Z
date_updated: 2026-09-24T10:26:59Z
day: '06'
ddc:
- '570'
department:
- _id: AnSa
doi: 10.1016/j.bpj.2023.12.020
ec_funded: 1
external_id:
  isi:
  - '001185235900001'
  pmid:
  - '38158654'
file:
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  checksum: 1c8fe1cf950394875b65b90da86428ff
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  creator: dernst
  date_created: 2024-07-16T12:09:55Z
  date_updated: 2024-07-16T12:09:55Z
  file_id: '17266'
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file_date_updated: 2024-07-16T12:09:55Z
fulldoi: https://doi.org/10.1016/j.bpj.2023.12.020
has_accepted_license: '1'
intvolume: '       123'
isi: 1
issue: '3'
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
page: 307-316
pmid: 1
project:
- _id: eba2549b-77a9-11ec-83b8-a81e493eae4e
  call_identifier: H2020
  grant_number: '802960'
  name: 'Non-Equilibrium Protein Assembly: from Building Blocks to Biological Machines'
publication: Biophysical Journal
publication_identifier:
  eissn:
  - 1542-0086
  issn:
  - 0006-3495
publication_status: published
publisher: Elsevier
quality_controlled: '1'
researchdata_availability: no
scopus_import: '1'
status: public
supplementarymaterial: no
title: Nonadditivity in interactions between three membrane-wrapped colloidal spheres
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: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 123
year: '2024'
...