Dynamic Force Patterns Promote Collective Cell Migration

Abstract

Embryonic wound repair is driven by collective cell migration into the wounded region. Contraction of a supracellular cable formed by actin and the motor protein non-muscle myosin II coordinates the cell movements that drive wound closure. We showed that, in Drosophila embryos, the actomyosin cable displays a heterogeneous pattern, with regions of high and low actin density. Mutants in which the distribution of actin is uniform around the wound display significantly slower wound healing. However, the mechanisms by which a non-uniform distribution of actin favors rapid wound repair are unknown. We used quantitative microscopy to investigate how the distribution of cytoskeletal molecules affects wound healing. We found that actin and myosin displayed matching heterogeneous distributions at the wound margin. Using laser ablation, we demonstrated that tension along the cable was correlated with actomyosin levels, indicating that contraction of the cable is non-uniform. A force balance showed that closure forces resulting at the interface between regions of high and low actomyosin contractility are greater than in regions of uniform contractility, suggesting that a non-uniform distribution of tension at the wound margin favors rapid wound repair. We developed an in silico model of wound repair, and we found that healing was faster when the pattern of tension along the wound margin was heterogeneous. Our model predicted that, to maintain a heterogeneous distribution of tension around the wound over time, the actomyosin pattern must change as cell boundaries deform. Consistent with this, we found that in vivo, myosin accumulates in segments of the wound margin that are stretched as a consequence of the contraction of adjacent, myosin-rich segments. Our results suggest that a non-uniform distribution of contractile forces along multicellular actomyosin networks generates mechanical signals that facilitate rapid network remodeling, and efficient collective cell movements.