Curvature-mediated bridging drives non-adhesive strip wound healing

Wound healing through re-epithelialization of gaps is of tremendous importance to the medical community. One critical mechanism identified by researchers for closing non-cell-adhesive gaps is the accumulation of actin cables around concave edges and the resulting purse string constriction. However, the studies to date have not separated the gap curvature effect from the gap size effect. Here, to investigate the strip edge curvature and strip size effects on the re-epithelialization responses of Madin-Darby canine kidney cells independently, we fabricate fibronectin micropatterned hydrogel substrates with straight and wavy non-cell-adhesive long strips of different radii of curvature and gap widths. Our experiments show that the epithelial cell re-epithelization is closely regulated by the gap geometry: actin cable accumulates at the two ends of straight stripes and drives gap closure via purse string contraction; straight strips do not facilitate cell migration perpendicular to wound front but wavy strips do, through the complex cell movement patterns induced by curved boundaries; cell bulging and lamellipodium extension can help establish bridges over gap widths in certain range, but not significantly beyond; for the gap size that can be bridged in the present study, actin cables can readily form to spread the bridges, leading to full gap closure. Our results can help to guide the development of better wound management strategies in the future.