Balance between cell-substrate adhesion and myosin contraction determines the frequency of motility initiation in fish keratocytes

Erin Barnhart, Kun Chun Lee, Greg M. Allen, Julie A. Theriot, Alex Mogilner

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Cells are dynamic systems capable of spontaneously switching among stable states. One striking example of this is spontaneous symmetry breaking and motility initiation in fish epithelial keratocytes. Although the biochemical and mechanical mechanisms that control steady-state migration in these cells have been well characterized, the mechanisms underlying symmetry breaking are less well understood. In this work, we have combined experimental manipulations of cell-substrate adhesion strength and myosin activity, traction force measurements, and mathematical modeling to develop a comprehensive mechanical model for symmetry breaking and motility initiation in fish epithelial keratocytes. Our results suggest that stochastic fluctuations in adhesion strength and myosin localization drive actin network flow rates in the prospective cell rear above a critical threshold. Above this threshold, high actin flow rates induce a nonlinear switch in adhesion strength, locally switching adhesions from gripping to slipping and further accelerating actin flow in the prospective cell rear, resulting in rear retraction and motility initiation. We further show, both experimentally and with model simulations, that the global levels of adhesion strength and myosin activity control the stability of the stationary state: The frequency of symmetry breaking decreases with increasing adhesion strength and increases with increasing myosin contraction. Thus, the relative strengths of two opposing mechanical forces - contractility and cell-substrate adhesion - determine the likelihood of spontaneous symmetry breaking and motility initiation.

Original languageEnglish (US)
Pages (from-to)5045-5050
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number16
DOIs
StatePublished - Apr 21 2015
Externally publishedYes

Keywords

  • Adhesion
  • Cell migration
  • Myosin
  • Symmetry breaking

ASJC Scopus subject areas

  • General

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