Geometry Adaptation of Protrusion and Polarity Dynamics in Confined Cell Migration

David B. Brückner, Matthew Schmitt, Alexandra Fink, Georg Ladurner, Johannes Flommersfeld, Nicolas Arlt, Edouard Hannezo, Joachim O. Rädler, Chase P. Broedersz*

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Cell migration in confining physiological environments relies on the concerted dynamics of several cellular components, including protrusions, adhesions with the environment, and the cell nucleus. However, it remains poorly understood how the dynamic interplay of these components and the cell polarity determine the emergent migration behavior at the cellular scale. Here, we combine data-driven inference with a mechanistic bottom-up approach to develop a model for protrusion and polarity dynamics in confined cell migration, revealing how the cellular dynamics adapt to confining geometries. Specifically, we use experimental data of joint protrusion-nucleus migration trajectories of cells on confining micropatterns to systematically determine a mechanistic model linking the stochastic dynamics of cell polarity, protrusions, and nucleus. This model indicates that the cellular dynamics adapt to confining constrictions through a switch in the polarity dynamics from a negative to a positive self-reinforcing feedback loop. Our model further reveals how this feedback loop leads to stereotypical cycles of protrusion-nucleus dynamics that drive the migration of the cell through constrictions. These cycles are disrupted upon perturbation of cytoskeletal components, indicating that the positive feedback is controlled by cellular migration mechanisms. Our data-driven theoretical approach therefore identifies polarity feedback adaptation as a key mechanism in confined cell migration.

Original languageEnglish
Article number031041
Pages (from-to)1-23
Number of pages23
JournalPhysical Review X
Volume12
Issue number3
Early online date20 Sept 2022
DOIs
Publication statusPublished - Sept 2022

Bibliographical note

Funding Information:
We thank Grzegorz Gradziuk, Steven Riedijk, Janni Harju, and M. R. Schnucki for helpful discussions, and Andriy Goychuk for advice on the image segmentation. This project was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), Project No. 201269156—SFB 1032 (Projects B01 and B12). D. B. B. is supported by the NOMIS Foundation and in part by a DFG fellowship within the Graduate School of Quantitative Biosciences Munich (QBM), as well as by the Joachim Herz Stiftung.

Publisher Copyright:
© 2022 authors. Published by the American Physical Society.

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