Dynamical Initiation of the Synergetic Migration in Epithelial Wound

Abstract

Wound closure is the major physiological events for maintaining and developing proper tissues. The cell migration along the boundaries of the wound closure have been categorized into two different modes: 1. Crawling migration with the lamellipodium extrusion, 2. Shrinking of wound edge due to the contractile force of multicellular actomyosin cables. These two migration modes proposed as complementary strategies that conduct exclusive work depending on the neighbor environment at first, but recent studies have reported the synergetic cooperation by two migration modes at the various curves of the wound. Interestingly, the large-scaled wound that was known for having only crawling migration in previous studies, also formed heterogeneous curvatures enough to generate the actin contractile force by making special features that named ‘‘fingering extrusion’’. Here, we focused on the role of the fingers in the wound healing with respect to the various sizes of the circular epithelial wound. At the small-sized wounds, cells showed a simple curve without fingers during the healing. However, at the large wound, the fingers extrusion occurred along the wound boundary with quite regular arrangements according to the size of wounds. This protrusion created various curvatures near the fingers, and the curvature sign of the cortical actin of cells determined the direction of contractile forces. So, the passively formed negative curvature by finger extrusions helped the cells moving to the vacancy with synergetic forces that from contraction and crawling. In addition, both the mathematical model and experimental model for the wound healing showed that the synergetic movement of cells depends on the proper distance and curvature between the two neighbor fingers. In conclusion, we identified the fingering extrusion as a trigger strategy for the earlier formation of effective migrations.