Dynamic force patterns promote collective cell movements during embryonic wound repair

Abstract

Embryonic wounds heal rapidly, in a process driven by coordinated cell movements. Polarization of actin and the molecular motor non-muscle myosin II in the cells adjacent to the wound results in the formation of a supracellular cable around the wound that drives repair. In Drosophila embryos, the distribution of actin around wounds is heterogeneous, with regions of high and low actin density, and actin heterogeneity is necessary for rapid repair. Here, we demonstrate that actin and myosin display stochastic patterns around embryonic wounds, and that contractile forces around wounds are heterogeneous. Mathematical modelling suggests that actomyosin heterogeneity favours wound closure if myosin is regulated by tension and strain, a hypothesis that we validate experimentally. We show that inhibition of stretch-activated ion channels disrupts myosin dynamics and tissue repair. Together, our results indicate that staggered contractile events, mechanical signals and force-regulated myosin dynamics coordinate cell behaviours to drive efficient wound closure. The motor proteins and contractile forces involved in wound closure are both shown to be heterogeneously distributed around a wound. Theory suggests that this heterogeneity speeds up wound closure, as long as the proteins are mechanically regulated.