Crawling cells can close wounds without purse strings or signaling.

Abstract

When a gash or gouge is made in a confluent layer of epithelial cells, the cells move to fill in the "wound." In some cases, such as in wounded embryonic chick wing buds, the movement of the cells is driven by cortical actin contraction (i.e., a purse string mechanism). In adult tissue, though, cells apparently crawl to close wounds. At the single cell level, this crawling is driven by the dynamics of the cell's actin cytoskeleton, which is regulated by a complex biochemical network, and cell signaling has been proposed to play a significant role in directing cells to move into the denuded area. However, wounds made in monolayers of Madin-Darby canine kidney (MDCK) cells still close even when a row of cells is deactivated at the periphery of the wound, and recent experiments show complex, highly-correlated cellular motions that extend tens of cell lengths away from the boundary. These experiments suggest a dominant role for mechanics in wound healing. Here we present a biophysical description of the collective migration of epithelial cells during wound healing based on the basic motility of single cells and cell-cell interactions. This model quantitatively captures the dynamics of wound closure and reproduces the complex cellular flows that are observed. These results suggest that wound healing is predominantly a mechanical process that is modified, but not produced, by cell-cell signaling.