Modeling the effect of vimentin on confined cell motility.

As a cell moves in a strongly confined geometry, its cytoskeleton undergoes changes as does the peri-nuclear cage. How do these changes affect cell motility? The cytoskeleton is made up of three different semi-flexible polymers: actin, microtubules, and intermediate filaments, such as vimentin. Recent studies demonstrate that the loss of vimentin enhances cell motility through micro-channels and confining spaces, though it has the opposite effect in 2D. We are, therefore, modeling the effects of intermediate filaments on cell motility in confinement to understand these latest experiments. We have developed a biophysical model for a cell moving through various confined geometries based on Brownian dynamics. It includes an intracellular network along with a peri-nuclear cage, both of which involve vimentin. We explore a possible mechanism behind the enhanced motility of vimentin-null cells, irrespective of channel width, in comparison to wild-type. We also characterize the increased speed of vimentin-null cells with increasing confinement and the minimal effect on the speed of wild-type cells under the same conditions. We also investigate the effects of flexible confinement walls on cell motility to better mimic the physiological conditions.