Computational model of 3D cell migration based on the molecular clutch mechanism

The external environment is a regulator of cell activity. Its stiffness and microstructure can either facilitate or prevent 3D cell migration in both physiology and disease. 3D cell migration results from force feedbacks between the cell and the extracellular matrix (ECM). Adhesions regulate these force feedbacks by working as molecular clutches that dynamically bind and unbind the ECM. Because of the interdependency between ECM properties, adhesion dynamics, and cell contractility, how exactly 3D cell migration occurs in different environments is not fully understood. In order to elucidate the effect of ECM on 3D cell migration through force-sensitive molecular clutches, we developed a computational model based on a lattice point approach. Results from the model show that increases in ECM pore size reduce cell migration speed. In contrast, matrix porosity increases it, given a sufficient number of ligands for cell adhesions and limited crowding of the matrix from cell replication. Importantly, these effects are maintained across a range of ECM stiffnesses’, demonstrating that mechanical factors are not responsible for how matrix microstructure regulates cell motility.