Geometric control by active mechanics of epithelial gap closure.

ABSTRACT

Epithelial wound healing is one of the most important biological processes occurring during the lifetime of an organism. It is a self-repair mechanism closing wounds or gaps within tissues to restore their functional integrity. In this work we derive a new diffuse interface approach for modelling the gap closure by means of a variational principle in the framework of non-equilibrium thermodynamics. We investigate the interplay between the crawling with lamellipodia protrusions and the supracellular tension exerted by the actomyosin cable on the closure dynamics. These active features are modeled as Korteweg forces into a generalised chemical potential. From an asymptotic analysis, we derive a pressure jump across the gap edge in the sharp interface limit. Moreover, the chemical potential diffuses as a Mullins-Sekerka system, and its interfacial value is given by a Gibbs-Thompson relation for its local potential driven by the curvature-dependent purse-string tension. The finite element simulations show an excellent quantitative agreement between the closure dynamics and the morphology of the edge with respect to existing biological experiments. The resulting force patterns are also in good qualitative agreement with existing traction force microscopy measurements. Our results shed light on the geometrical control of the gap closure dynamics resulting from the active forces that are chemically activated around the gap edge.