Cooperativity of cell crawling and active contractility regulates gap closure efficiency in tissues*

Many developmental processes, such as morphogenesis, wound repair, and apoptosis, involve the closure of tissue gaps to maintain mechanical integrity. Depending on the environment, gap closure is mediated by lamellipodial cell crawling, or by purse-string based contraction of a multicellular actomyosin cable. To investigate how these processes collectively regulate the rate of wound repair, we introduce a cell-based computational model for a wounded monolayer adherent to a soft substrate. By systematically varying substrate stiffness, wound geometry, and intercellular cohesion, we show that a mixture of purse-string and crawling is always efficient for faster gap closure, irrespective of cell and substrate properties. We find that substrate rigidity and tissue fluidity enhances the rate of wound repair, suggesting that the assembly of purse-string and lamellipodia are mechanosensitive. While crawling driven closure occurs at a constant speed, we find purse-string based closure is strongly sensitive to gap geometry. These results suggest that wounded tissues can modulate their cytoskeletal machineries in an adaptive manner to repair wounds efficiently in diverse environments.