Mechanical interactions among followers determine the emergence of leaders in 
migrating epithelial cell collectives

Vishwakarma, Medhavi; Di Russo, Jacopo; Probst, Dimitri; Schwarz, Ulrich S.; Das, Tamal; Spatz, Joachim P.

doi:10.1038/s41467-018-05927-6

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Mechanical interactions among followers determine the emergence of leaders in migrating epithelial cell collectives

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Vishwakarma, Medhavi
Cellular Biophysics, Max Planck Institute for Medical Research, Max Planck Society;
Biophysical Chemistry, Institute of Physical Chemistry, University of Heidelberg, 69120 Heidelberg, Germany;

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Di Russo, Jacopo
Cellular Biophysics, Max Planck Institute for Medical Research, Max Planck Society;
Biophysical Chemistry, Institute of Physical Chemistry, University of Heidelberg, 69120 Heidelberg, Germany;

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Das, Tamal
Cellular Biophysics, Max Planck Institute for Medical Research, Max Planck Society;
Biophysical Chemistry, Institute of Physical Chemistry, University of Heidelberg, 69120 Heidelberg, Germany;

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Spatz, Joachim P.
Cellular Biophysics, Max Planck Institute for Medical Research, Max Planck Society;
Biophysical Chemistry, Institute of Physical Chemistry, University of Heidelberg, 69120 Heidelberg, Germany;

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Citation

Vishwakarma, M., Di Russo, J., Probst, D., Schwarz, U. S., Das, T., & Spatz, J. P. (2018). Mechanical interactions among followers determine the emergence of leaders in migrating epithelial cell collectives. Nature Communications, 9(1): 3469, pp. 1-12. doi:10.1038/s41467-018-05927-6.

Cite as: https://hdl.handle.net/21.11116/0000-0002-05C6-9

Abstract

Regulating the emergence of leaders is a central aspect of collective cell migration, but the underlying mechanisms remain ambiguous. Here we show that the selective emergence of leader cells at the epithelial wound-margin depends on the dynamics of the follower cells and is spatially limited by the length-scale of collective force transduction. Owing to the dynamic heterogeneity of the monolayer, cells behind the prospective leaders manifest locally increased traction and monolayer stresses much before these leaders display any phenotypic traits. Followers, in turn, pull on the future leaders to elect them to their fate. Once formed, the territory of a leader can extend only to the length up-to which forces are correlated, which is similar to the length up-to which leader cells can transmit forces. These findings provide mechanobiological insight into the hierarchy in cell collectives during epithelial wound healing.