Multiscale Modeling of MT1-MMP-Mediated Cell Migration: Destabilization of Cell-Matrix Adhesion

Abstract

One of several ways MT1-MMP promotes cell migration is by modifying cell adhesion properties. MT1-MMP directly processes cell adhesion properties by shedding cell transmembrane receptors that attach cells to the extracellular matrix (ECM). The shedding leads to the destabilization and disassembly of firm cell-matrix adhesion that holds cells in their stationary position, prompting cells to migrate. In this paper, we present a multiscale mathematical model of single cell migration driven by MT1-MMP destabilization of cell-matrix adhesion. The dynamics of MT1-MMP are modeled using a system of differential equations that are integrated with the Cellular Potts Model (CPM) for a combined modeling at the intracellular and cellular scale, respectively. The CPM is extended to include a local feedback mechanism from MT1-MMP on the membrane that enhances cell membrane fluctuations, resulting in actively migrating cells. The results of computational simulation show that MT1-MMP is capable of destabilizing strong cell-matrix adhesion and stimulating cell migration, and at the same time, also producing cell polarization and motile cell morphology.