Border forces and friction control epithelial closure dynamics

Abstract

Epithelization, the process whereby an epithelium covers a cell-free surface, is not only central to wound healing but also pivotal in embryonic morphogenesis, regeneration, and cancer. In the context of wound healing, the epithelization mechanisms differ depending on the sizes and geometries of the wounds as well as on the cell type while a unified theoretical decription is still lacking. Here, we used a barrier-based protocol that allows for making large arrays of well-controlled circular model wounds within an epithelium at confluence, without injuring any cells. We propose a physical model that takes into account border forces, friction with the substrate, and tissue rheology. Despite the presence of a contractile actomyosin cable at the periphery of the wound, epithelization was mostly driven by border protrusive activity. Closure dynamics was quantified by an epithelization coefficient $D = \sigma_p/\xi$ defined as the ratio of the border protrusive stress $\sigma_p$ to the friction coefficient $\xi$ between epithelium and substrate. The same assay and model showed a high sensitivity to the RasV12 mutation on human epithelial cells, demonstrating the general applicability of the approach and its potential to quantitatively characterize metastatic transformations.Comment: 44 pages, 17 figure