Vimentin mediates nuclear shape and position to affect cell speed and polarity in confinement.

The ability of cells to move through small spaces depends on the mechanical properties of the cellular cytoskeleton and nuclear deformability. The cytoskeleton is comprised of three interacting, semi-flexible polymer networks: actin, microtubules, and intermediate filaments (IF). Vimentin is an IF protein that protects the cell nucleus from damage and provides elasticity to the cytoskeleton, but its role in how cells move through confining 3D spaces remains unclear. We develop a minimal model of cells moving through confined geometries that effectively includes all three types of cytoskeletal filaments. We find that increased bulk cytoskeletal stiffness, due to vimentin coupling to the actin cortex, leads to more deformed nuclei and decreased cell speed for channel geometries approximately less than the width of a cell. Vimentin also allows for more efficient stress transmission between the cell cortex and the nucleus to more readily control the position of the nucleus within the cell. We posit that as the nucleus position deviates further from the center of mass of the cell, microtubules become more oriented in a particular direction to enhance cell polarity. We provide a quantitative interpretation for recent cell motility experiments with and without vimentin