Dynamic Force Patterns Promote Collective Cell Migration

Teresa Zulueta-Coarasa 1, 2 ;  Rodrigo Fernandez-Gonzalez 1, 2, 3, 4

1. Institute of Biomaterials and Biomedical Engineering, University of Toronto.; 2. Ted Rogers Centre for Heart Research, University of Toronto.; 3. Department of Cell and Systems Biology, University of Toronto.; 4. Developmental and Stem Cell Biology Program, The Hospital for Sick Children.

Embryos display an outstanding ability to rapidly repair wounds, in a process driven by collective cell movements. Upon wounding, actin and the motor protein non-muscle myosin II become polarized in the cells adjacent to the lesion, forming a supracellular cable around the wound. Cable contraction drives tissue repair. We showed that, in Drosophila embryos, the cable is heterogeneous, with regions of high and low actin density. Mutants in which actin is uniform around the wound display slower wound closure. However, the mechanisms by which a non-uniform distribution of actin favours rapid repair are unknown. Using laser ablation, we demonstrated that actomyosin-rich segments sustain higher contractile forces, indicating that cable contraction is non-uniform. Contraction was faster in heterogeneous than in homogeneous segments of the cable. We developed a computer model of wound repair, and we found that a heterogeneous actomyosin distribution was favourable for wound closure when myosin assembly at the wound edge was strain-dependent. We found that myosin rapidly accumulated in vivo in segments of the wound margin that were stretched as a consequence of the contraction of adjacent segments. Furthermore, interfaces at the wound margin that were mechanically isolated from their neighbours failed to accumulate myosin. Finally, we used a laser-based method to induce ectopic strain on cell boundaries, and we found that myosin accumulated in response to deformation. Our results suggest that local actomyosin heterogeneities promote faster interfacial contraction, and that a non-uniform distribution of contractile forces along multicellular actomyosin networks generates mechanical signals that facilitate myosin assembly and efficient collective cell movements.