Migration dynamics and model of cells crawling on a matrix with cell-scale stiffness heterogeneity

In living tissues where cells migrate, spatial distribution of mechanical properties, especially matrix stiffness, are generally heterogenous with cell-scales ranging from 10 to 1000 μm. Since the cell migration in our body plays critical role in morphogenesis, wound healing, and cancer metastasis, it is essential to understand the migratory dynamics on the matrix with cell-scale stiffness heterogeneity. However, while cellular responses to homogeneous matrix have been extensively explored, studies of the cell motility with stiffness heterogeneity have been limited to the directional movement (durotaxis) driven by a simple stiffness gradient. Thus, we need to elucidate how cell migration is determined through the interaction among cell-scale stiffness heterogeneity and cellular responses such as dynamics of the cell-matrix adhesion site, the intracellular prestress, and cell shape.

In this talk, we introduce our experiments on cell motility, shaping, adhesion, and traction forces at long time scales using microelastically patterned hydrogels that enable us to systematically control the cell-scale heterogeneity of the matrix-stiffness. Using microelastically patterned hydrogels, we showed that the cell exhibited a general mode of durotaxis depending on the shape and size of the stiff domains, which was coincided with the extraordinarily large fluctuation of the traction force. We proposed a cell migration model based on equations of a deformable self-propelled particle adopting an amoeboid swimmer-like velocity-shape relationship. By considering the cellular response to stiffness gradients, the model can reproduce general durotaxis driven by cell-scale heterogeneity of the matrix-stiffness.