Loss of vimentin intermediate filaments decreases peri-nuclear stiffness and enhances cell motility through confined spaces

TL;DR

This study shows that vimentin intermediate filaments increase perinuclear stiffness and reduce cell motility through confined spaces, revealing a mechanical role in cell migration.

Contribution

It demonstrates how vimentin influences cell stiffness and motility, highlighting its mechanical function in cell migration through tight environments.

Findings

Loss of vimentin increases cell motility in confined spaces.

Vimentin enhances perinuclear stiffness of cells.

Vimentin's effect on stiffness depends on extracellular matrix signaling.

Abstract

The migration of cells through tight constricting spaces or along fibrous tracks in tissues is important for biological processes, such as embryogenesis, wound healing, and cancer metastasis, and depends on the mechanical properties of the cytoskeleton. Migratory cells often express and upregulate the intermediate filament protein vimentin. The viscoelasticity of vimentin networks in shear deformation has been documented, but its role in motility is largely unexplored. Here, we studied the effects of vimentin on cell motility and stiffness using mouse embryo fibroblasts derived from wild-type and vimentin-null mice. We find that loss of vimentin increases motility through small pores and along thin capillaries. Atomic force microscopy measurements reveal that the presence of vimentin enhances the perinuclear stiffness of the cell, to an extent that depends on surface ligand presentation and therefore signaling from extracellular matrix receptors. Together, our results indicate that vimentin hinders three-dimensional motility by providing mechanical resistance against large strains and may thereby protect the structural integrity of cells.