Collective cell migration offers a rich field of study for non-equilibrium physics and cellular biology, revealing phenomena such as glassy dynamics, pattern formation and active turbulence. However, how mechanical and chemical signalling are integrated at the cellular level to give rise to such collective behaviours remains unclear. We address this by focusing on the highly conserved phenomenon of spatiotemporal waves of density and extracellular signal-regulated kinase (ERK) activation, which appear both in vitro and in vivo during collective cell migration and wound healing. First, we propose a biophysical theory, backed by mechanical and optogenetic perturbation experiments, showing that patterns can be quantitatively explained by a mechanochemical coupling between active cellular tensions and the mechanosensitive ERK pathway. Next, we demonstrate how this biophysical mechanism can robustly induce long-ranged order and migration in a desired orientation, and we determine the theoretically optimal wavelength and period for inducing maximal migration towards free edges, which fits well with experimentally observed dynamics. We thereby provide a bridge between the biophysical origin of spatiotemporal instabilities and the design principles of robust and efficient long-ranged migration.
We would like to thank G. Tkacik and all of the members of the Hannezo and Hirashima groups for useful discussions, X. Trepat for help on traction force microscopy and M. Matsuda for use of the lab facility. E.H. acknowledges grants from the Austrian Science Fund (FWF) (P 31639) and the European Research Council (851288). T.H. acknowledges a grant from JST, PRESTO (JPMJPR1949). This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 665385 (to D.B.), from JSPS KAKENHI grant no. 17J02107 (to N.H.) and from the SPIRITS 2018 of Kyoto University (to E.H. and T.H.).
Boocock DR, Hino N, Ruzickova N, Hirashima T, Hannezo EB. Theory of mechanochemical patterning and optimal migration in cell monolayers. Nature Physics. 2020. doi:10.1038/s41567-020-01037-7
Boocock, D. R., Hino, N., Ruzickova, N., Hirashima, T., & Hannezo, E. B. (2020). Theory of mechanochemical patterning and optimal migration in cell monolayers. Nature Physics. https://doi.org/10.1038/s41567-020-01037-7
Boocock, Daniel R, Naoya Hino, Natalia Ruzickova, Tsuyoshi Hirashima, and Edouard B Hannezo. “Theory of Mechanochemical Patterning and Optimal Migration in Cell Monolayers.” Nature Physics, 2020. https://doi.org/10.1038/s41567-020-01037-7.
D. R. Boocock, N. Hino, N. Ruzickova, T. Hirashima, and E. B. Hannezo, “Theory of mechanochemical patterning and optimal migration in cell monolayers,” Nature Physics, 2020.
Boocock DR, Hino N, Ruzickova N, Hirashima T, Hannezo EB. 2020. Theory of mechanochemical patterning and optimal migration in cell monolayers. Nature Physics.
Boocock, Daniel R., et al. “Theory of Mechanochemical Patterning and Optimal Migration in Cell Monolayers.” Nature Physics, Springer Nature, 2020, doi:10.1038/s41567-020-01037-7.
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