Mapping cytoskeletal stress concentrations and nuclear stresses during confined cell migration

Cell migration through dense matrices is accompanied by an increase in perinuclear F-actin intensity in the cytoplasm across multiple cell-types. However, it is yet unclear whether stress concentrations are instrumental in determining spatial distribution of F-actin. In this study, using a finite element model, we investigate the spatial stress evolution within the cytoplasm during confined cell migration as a function of degree of confinement, tissue stiffness and nuclear stiffness. Stress analysis of confined cell migration revealed stress concentrations at perinuclear regions at sites of high nuclear curvature in a pore size-dependent and tissue stiffness-dependent manner. While perinuclear stresses were found to depend on the ratio of nuclear to tissue stiffness, the magnitude of stresses inside the nucleus are dictated by nuclear stiffness. In addition to identifying cytoplasmic stress distributions as a factor in governing the spatial localization of perinuclear F-actin during confined cell migration, our results suggest that nuclear stiffness and tissue stiffness collectively determine the efficiency of confined migration by modulating the extent of nuclear deformation and the magnitude of nuclear stresses.