(A-36) Geometry-mediated Bridging Drives Wound Healing of Nonadhesive Stripes

Introduction:: Re-epithelialization is a critical process for the repair of damaged epithelial tissues during wound healing and therefore is of profound importance to the medical community. This process involves coordinated collective migration of epithelial cells and is closely mediated by wound geometry. 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-edge curvature effect from the gap size effect.


Materials and Methods:: To separate the gap-edge curvature and gap size effects, we fabricate micropatterned hydrogel substrates with long non-cell-adhesive stripes that are either straight or wavy. The radius of curvature and gap width are varied systematically to investigate the stripe edge curvature and stripe width effects on the reepithelialization of Madin–Darby canine kidney (MDCK) cells. The collective migration of MDCK cells is monitored using time-lapse microscopy.


Results, Conclusions, and Discussions:: Our results show that MDCK cell reepithelization is closely regulated by the gap geometry and may occur through different pathways. In addition to purse-string contraction, we identify gap bridging either via cell protrusion or by lamellipodium extension as critical cellular and molecular mechanisms for wavy gap closure. Cell migration in the direction perpendicular to wound front, sufficiently small gap size to allow bridging, and sufficiently high negative curvature at cell bridges for actin cable constriction are necessary/sufficient conditions for gap closure. Our experiments demonstrate that straight stripes rarely induce cell migration perpendicular to wound front, but wavy stripes do; cell protrusion and lamellipodia extension can help establish bridges over gaps of about five times the cell size, but not significantly beyond. Such discoveries deepen our understanding of mechanobiology of cell responses to curvature and help guide development of biophysical strategies for tissue repair, plastic surgery, and better wound management.


Acknowledgements (Optional): : C.H. acknowledges financial support from Ministry of Education (MOE), Singapore, under its Academic Research Fund Tier 2 (MOET2EP50121-0004).

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