Continuum Model of Collective Cell Migration in Wound Healing and Colony Expansion

AbstractCollective cell migration plays an important role during wound healing and embryo development. Although the exact mechanisms that coordinate such migration are still unknown, experimental studies of moving cell layers have shown that the primary interactions governing the motion of the layer are the force of lamellipodia, the adhesion of cells to the substrate, and the adhesion of cells to each other. Here, we derive a two-dimensional continuum mechanical model of cell-layer migration that is based on a novel assumption of elastic deformation of the layer and incorporates basic mechanical interactions of cells as well as cell proliferation and apoptosis. The evolution equations are solved numerically using a level set method. The model successfully reproduces data from two types of experiments: 1), the contraction of an enterocyte cell layer during wound healing; and 2), the expansion of a radially symmetric colony of MDCK cells, both in the edge migration velocity and in cell-layer density. In accord with experimental observations, and in contrast to reaction-diffusion models, this model predicts a partial wound closure if lamellipod formation is inhibited at the wound edge and gives implications of the effect of spatially restricted proliferation