Computational modeling and simulation of epithelial wound closure

Abstract

Wounds in the epithelium may lead to serious injurious events or chronic inflammatory diseases, however, multicellular organisms have the ability to self-repair wounds through the movement of epithelial cell toward the wound area. Despite intensive studies exploring the mechanism of wound closure, the role of mechanics in epithelial wound closure is still not well explained. In order to investigate the role of mechanical properties on wound closure process, a three-dimensional continuum physics-based computational model is presented in this study. The model takes into account the material property of the epithelial cell, intercellular interactions between neighboring cells at cell–cell junctions, and cell-substrate adhesion between epithelial cells and ECM. Through finite element simulation, it is found that the closure efficiency is related to the initial gap size and the intensity of lamellipodial protrusion. It is also shown that cells at the wound edge undergo higher stress compared with other cells in the epithelial monolayer, and the cellular normal stress dominates over the cellular shear stress. The model presented in this study can be employed as a numerical tool to unravel the mechanical principles behind the complex wound closure process. These results might have the potential to improve effective wound management and optimize the treatment.