Computational study of local and global ECM degradation and the effects on cell speed and cell–matrix tractions

Abstract

Cell migration is important to biological processes such as wound healing and cancer invasion. Cell movement involves forming bonds between cell surface receptors and ligands present in the extracellular matrix (ECM) in order to generate the necessary forces on the matrix. For three-dimensional cell migration, partial degradation of the adjacent ECM using matrix metalloproteinases is necessary to create a passage with less motion resistance. Our mathematical model takes into consideration cell–ECM tractions needed to drive cell movement, viscous drag forces, and a transient matrix degradation process. Simulations were performed for global and highly localized matrix degradation processes, where the latter occurred at the cell–ECM interface. It was observed that the higher the speed of the cell boundary, the higher the matrix concentration after localized degradation. The results showed that a greater ECM degradation coefficient was needed for optimal cell migration to occur for the local process and that cell–ECM tractions were larger. The results from this investigation complement those obtained by other studies where it has been shown that cell speed is a biphasic function of ligand and matrix metalloproteinase concentration, and would also be of use for research on wound healing, cancer cell invasion, and tissue engineering.