Substrate stiffness regulates cadherin-dependent collective migration through myosin-II contractility

Mei Rosa Ng, Achim Besser, Gaudenz Danuser, Joan S. Brugge

Research output: Contribution to journalArticle

163 Scopus citations

Abstract

The mechanical microenvironment is known to influence single-cell migration; however, the extent to which mechanical cues affect collective migration of adherent cells is not well understood. We measured the effects of varying substrate compliance on individual cell migratory properties in an epithelial wound-healing assay. Increasing substrate stiffness increased collective cell migration speed, persistence, and directionality as well as the coordination of cell movements. Dynamic analysis revealed that wounding initiated a wave of motion coordination from the wound edge into the sheet. This was accompanied by a front-to-back gradient of myosin-II activation and establishment of cell polarity. The propagation was faster and farther reaching on stiff substrates, indicating that substrate stiffness affects the transmission of directional cues. Manipulation of myosin-II activity and cadherin-catenin complexes revealed that this transmission is mediated by coupling of contractile forces between neighboring cells. Thus, our findings suggest that the mechanical environment integrates in a feedback with cell contractility and cell-cell adhesion to regulate collective migration.

Original languageEnglish (US)
Pages (from-to)545-563
Number of pages19
JournalJournal of Cell Biology
Volume199
Issue number3
DOIs
StatePublished - Oct 1 2012

ASJC Scopus subject areas

  • Cell Biology

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