Cellular mechanics of wound formation in single cell layer under cyclic stretching

Wounds can be produced when cells and tissues are subjected to excessive forces, for instance, under pathological conditions or nonphysiological loading. However, the cellular behaviors in the wound formation process are not clear. Here we tested the behaviors of wound formation in the epithelial layer with an in-suit uniaxial stretching device. We found that the wound often nucleates at the position where the cells are dividing. The polarization direction of cells near the wound is preferentially along the wound edge, whereas the cells far from the wound are preferentially perpendicular to the stretching direction. The larger the wound area is, the higher is the aspect ratio of the cells around the wound. Increasing the cell density will strengthen the cell layer. The higher the cell density is, the smaller is the area of the wounds, and the weaker is the effect of stretching on the polarization of the cells. Furthermore, we built a coarse-grained cell model that can explicitly consider the elasticity and viscoelasticity of cells, cell-cell interaction, and cell active stress, by which we simulated the wound formation process and quantitatively analyzed the force and stress fields in the cell layer, particularly around the wound. These analyses reveal the cellular mechanisms of wound formation behaviors in the cell layer under stretching and shed useful light on tissue engineering and regenerative medicine for biomedical applications.