A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Self-generated chemotaxis of mixed cell populations
Tekijät: Ucar, Mehmet Can; Alsberga, Zane; Alanko, Jonna; Sixt, Michael; Hannezo, Edouard
Kustantaja: Proceedings of the National Academy of Sciences
Julkaisuvuosi: 2025
Lehti:: Proceedings of the National Academy of Sciences of the United States of America
Artikkelin numero: e2504064122
Vuosikerta: 122
Numero: 34
ISSN: 0027-8424
eISSN: 1091-6490
DOI: https://doi.org/10.1073/pnas.2504064122
Verkko-osoite: https://doi.org/10.1073/pnas.2504064122
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/500228839
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.
Julkaisussa olevat rahoitustiedot:
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 from the European Research Council under the European Union's Horizon 2020 research and innovation program (grant agreement No. 851288to E.H.). M.C.U. is funded by a University of Sheffield Strategic Research Fellowship in the Physics of Life and Quantitative Biology.
