A mechanobiological model to study upstream cell migration guided by tensotaxis

Cell migration is a process of crucial importance for the human body. It is responsible for important processes such as wound healing and tumor metastasis. Migration may occur in response to stimuli of chemical, physical and mechanical nature occurring in the cellular microenvironment. The interstitial flow (IF) can generate mechanical stimuli in cells that influence the cell behavior and interactions of the cells with the extracellular matrix (ECM). One of the phenomena is upstream migration, which is observed in some tumors. In this work, we present a new approach to study the adherent cell migration in a porous medium using a mechanobiological model, attempting to understand if upstream migration can be generated exclusively by mechanical factors. The influence of IF on the behavior of cells and the extracellular matrix was considered. The model is based on a system of coupled nonlinear differential equations solved by the finite element method. Several simulations were performed to study the upstream cell migration and evaluate the effects of pressure, permeability, ECM stiffness and cellular concentration variations on the cell velocity. The results indicated that upstream migration can occur in the presence of mechanical stimuli generated by IF and that the tested parameters have a direct influence on the cellular velocity, especially the pressure and the permeability.