Cell Mechanics at the Rear Act To Steer the Direction of Cell Migration

Abstract

SummaryMotile cells navigate complex environments by changing their direction of travel, generating left-right asymmetries in their mechanical subsystems to physically turn. Currently little is known about how external directional cues are propagated along the length scale of the whole cell and integrated with its force-generating apparatus to steer migration mechanically. We examine the mechanics of spontaneous cell turning in fish epidermal keratocytes and find that the mechanical asymmetries responsible for turning behavior predominate at the rear of the cell, where there is asymmetric centripetal actin flow. Using experimental perturbations we identify two linked feedback loops connecting myosin II contractility, adhesion strength and actin network flow in turning cells that are sufficient to recreate observed cell shapes and trajectories in a computational model. Surprisingly, asymmetries in actin polymerization at the cell leading edge play only a minor role in the mechanics of cell turning – that is, cells steer from the rear.HighlightsFish keratocytes can migrate with persistent angular velocity, straight or in circles.Asymmetry in protrusion at the leading edge is not sufficient to generate persistent turning.Asymmetries in myosin II contraction, actin flow and adhesion at the cell rear cause turns.Our new computational model of migration predicts observed cell trajectories.