Tractions and Stress Fibers Control Cell Shape and Rearrangements in Collective Cell Migration

Abstract

Key to collective cell migration is the ability of cells to rearrange their position with respect to their neighbors. Recent theory and experiments demonstrated that cellular rearrangements are facilitated by cell shape, with cells having more elongated shapes and greater perimeters more easily sliding past their neighbors within the cell layer. Though it is thought that cell perimeter is controlled primarily by cortical tension and adhesion at each cell's periphery, experimental testing of this hypothesis has produced conflicting results. Here we studied collective cell migration in an epithelial monolayer by measuring forces, cell perimeters, and motion, and found all three to decrease with either increased cell density or inhibition of cell contraction. In contrast to previous understanding, the data suggest that cell shape and rearrangements are controlled not by cortical tension or adhesion at the cell periphery but rather by the stress fibers that produce tractions at the cell-substrate interface. This finding is confirmed by an experiment showing that increasing tractions reverses the effect of density on cell shape and rearrangements. Our study therefore reduces the focus on the cell periphery by establishing cell-substrate traction as a major physical factor controlling cell shape and motion in collective cell migration.