---
OA_place: publisher
OA_type: hybrid
PlanS_conform: '1'
_id: '20289'
abstract:
- lang: eng
text: Cell and tissue movement in development, cancer invasion, and immune response
relies on chemical or mechanical guidance cues. In many systems, this behavior
is locally directed by self-generated signaling gradients rather than long-range,
prepatterned cues. However, how heterogeneous mixtures of cells interact nonreciprocally
and navigate through self-generated gradients remains largely unexplored. Here,
we introduce a theoretical framework for the self-organized chemotaxis of heterogeneous
cell populations. We find that the relative chemotactic sensitivities of different
cell populations control their long-time coupling and comigration dynamics, with
boundary conditions such as external cell and attractant reservoirs substantially
influencing the migration patterns. Our model predicts an optimal parameter regime
that enables robust and colocalized migration. We test our theoretical predictions
with in vitro experiments demonstrating the comigration of distinct immune cell
populations, and quantitatively reproduce observed migration patterns under wild-type
and perturbed conditions. Interestingly, immune cell comigration occurs close
to the predicted optimal regime. Finally, we incorporate mechanical interactions
into our framework, revealing a nontrivial interplay between chemotactic and mechanical
nonreciprocity in driving collective migration. Together, our findings suggest
that self-generated chemotaxis is a robust strategy for the navigation of mixed
cell populations.
acknowledged_ssus:
- _id: Bio
- _id: PreCl
- _id: LifeSc
- _id: NanoFab
acknowledgement: We thank all members of the M.S. and E.H. groups for stimulating
discussions.We thank the Imaging and Optics facility, the Pre-clinical and Lab Support
facility of the Institute of Science and Technology Austria for their excellent
support and provided resources for the experimental research. In particular, we
thank Jack Merrin from the Nanofabrication facility who generated the microfabricated
channel used in this study. This work received funding fromt he European Research
Council under the European Union’s Horizon 2020 research and innovation program
(grant agreement No. 851288 to E.H.). M.C.U.is funded by a University of Sheffield
Strategic Research Fellowship in the Physics of Life and Quantitative Biology.
article_number: e2504064122
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Mehmet C
full_name: Ucar, Mehmet C
id: 50B2A802-6007-11E9-A42B-EB23E6697425
last_name: Ucar
orcid: 0000-0003-0506-4217
- first_name: Alsberga
full_name: Zane, Alsberga
id: 60f7509a-f652-11ea-9d86-b963d6490d7c
last_name: Zane
orcid: 0009-0003-0415-7603
- 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: 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: Ucar MC, Zane A, Alanko JH, Sixt MK, Hannezo EB. Self-generated chemotaxis
of mixed cell populations. Proceedings of the National Academy of Sciences.
2025;122(34). doi:10.1073/pnas.2504064122
apa: Ucar, M. C., Zane, A., Alanko, J. H., Sixt, M. K., & Hannezo, E. B. (2025).
Self-generated chemotaxis of mixed cell populations. Proceedings of the National
Academy of Sciences. National Academy of Sciences. https://doi.org/10.1073/pnas.2504064122
chicago: Ucar, Mehmet C, Alsberga Zane, Jonna H Alanko, Michael K Sixt, and Edouard
B Hannezo. “Self-Generated Chemotaxis of Mixed Cell Populations.” Proceedings
of the National Academy of Sciences. National Academy of Sciences, 2025. https://doi.org/10.1073/pnas.2504064122.
ieee: M. C. Ucar, A. Zane, J. H. Alanko, M. K. Sixt, and E. B. Hannezo, “Self-generated
chemotaxis of mixed cell populations,” Proceedings of the National Academy
of Sciences, vol. 122, no. 34. National Academy of Sciences, 2025.
ista: Ucar MC, Zane A, Alanko JH, Sixt MK, Hannezo EB. 2025. Self-generated chemotaxis
of mixed cell populations. Proceedings of the National Academy of Sciences. 122(34),
e2504064122.
mla: Ucar, Mehmet C., et al. “Self-Generated Chemotaxis of Mixed Cell Populations.”
Proceedings of the National Academy of Sciences, vol. 122, no. 34, e2504064122,
National Academy of Sciences, 2025, doi:10.1073/pnas.2504064122.
short: M.C. Ucar, A. Zane, J.H. Alanko, M.K. Sixt, E.B. Hannezo, Proceedings of
the National Academy of Sciences 122 (2025).
corr_author: '1'
date_created: 2025-09-07T22:01:32Z
date_published: 2025-08-26T00:00:00Z
date_updated: 2026-02-16T12:31:05Z
day: '26'
ddc:
- '570'
department:
- _id: EdHa
- _id: MiSi
doi: 10.1073/pnas.2504064122
ec_funded: 1
external_id:
isi:
- '001562181600001'
pmid:
- '40838890'
file:
- access_level: open_access
checksum: b36abd92673b6d76376fc9434bad52cc
content_type: application/pdf
creator: dernst
date_created: 2025-09-08T07:23:29Z
date_updated: 2025-09-08T07:23:29Z
file_id: '20307'
file_name: 2025_PNAS_Ucar.pdf
file_size: 16069140
relation: main_file
success: 1
file_date_updated: 2025-09-08T07:23:29Z
has_accepted_license: '1'
intvolume: ' 122'
isi: 1
issue: '34'
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 05943252-7A3F-11EA-A408-12923DDC885E
call_identifier: H2020
grant_number: '851288'
name: Design Principles of Branching Morphogenesis
publication: Proceedings of the National Academy of Sciences
publication_identifier:
eissn:
- 1091-6490
issn:
- 0027-8424
publication_status: published
publisher: National Academy of Sciences
quality_controlled: '1'
related_material:
link:
- relation: software
url: https://github.com/mehmetcanucar/Self-generated-chemotaxis
scopus_import: '1'
status: public
title: Self-generated chemotaxis of mixed cell populations
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: 122
year: '2025'
...