Synergy of Cells and Substrate in Cell Migration

Cell migration is a coordinated process that is ubiquitous in biology and plays a significant role in biological processes, such as morphogenesis, cancer metastasis, and tissue repair. To illuminate mechanisms of cell migration within a unified framework, we developed a versatile, computational model for cell migration on 2D substrates. The model incorporates lamellipodial dynamics as well as mechanical interaction between cells and substrate in a rigorous manner. We employed the model to recapitulate various aspects of individual and collective cell migration on deformable or stiff substrates. The model shows how persistent random walk is regulated at early and late stages. We show how durotaxis originates in mechanical interactions between cells and substrate; and how cells follow substrate alignment as contact guidance. We explain contact-inhibition of locomotion in a new way, and show how the collective migration behavior varies with cell density. Finally, we simulate how mechanical properties of deformable substrates dictate the evolution and patterning of cell ensembles. The predictive ability of this model can provide critical insights into diverse physiological and pathological phenomena.