  The ability of cells to move through small spaces depends on the mechanical
properties of the cellular cytoskeleton and on nuclear deformability. In
mammalian cells, the cytoskeleton is comprised of three interacting,
semi-flexible polymer networks: actin, microtubules, and intermediate filaments
(IF). Recent experiments of mouse embryonic fibroblasts with and without
vimentin have shown that the IF vimentin plays a role in confined cell
motility. We, therefore, develop a minimal model of cells moving through
confined geometries that effectively includes all three types of cytoskeletal
filaments with a cell consisting of an actomyosin cortex and a deformable cell
nucleus and mechanical connections between the two cortices the outer
actomyosin one and the inner nuclear one. By decreasing the amount of vimentin,
we find that the cell speed is typically faster for vimentin-null cells as
compared to cells with vimentin. Vimentin-null cells also contain more deformed
nuclei in confinement. Finally, vimentin affects nucleus positioning within the
cell. By positing 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 persistence or polarity, we show that vimentin-nulls
are more persistent than vimentin-full cells. The enhanced persistence
indicates that the vimentin-null cells are more subjugated by the confinement
since their internal polarization mechanism that depends on cross-talk of the
centrosome with the nucleus and other cytoskeletal connections is diminished.
In other words, the vimentin-null cells rely more heavily on external cues. Our
modeling results present a quantitative interpretation for recent experiments
and have implications for understanding the role of vimentin in the
epithelial-mesenchymal transition.
