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The migration of cells through tight constricting spaces or along fibroustracks in tissues is important for biological processes, such as embryogenesis,wound healing, and cancer metastasis, and depends on the mechanical propertiesof the cytoskeleton. Migratory cells often express and upregulate theintermediate filament protein vimentin. The viscoelasticity of vimentinnetworks in shear deformation has been documented, but its role in motility islargely unexplored. Here, we studied the effects of vimentin on cell motilityand stiffness using mouse embryo fibroblasts derived from wild-type andvimentin-null mice. We find that loss of vimentin increases motility throughsmall pores and along thin capillaries. Atomic force microscopy measurementsreveal that the presence of vimentin enhances the perinuclear stiffness of thecell, to an extent that depends on surface ligand presentation and thereforesignaling from extracellular matrix receptors. Together, our results indicatethat vimentin hinders three-dimensional motility by providing mechanicalresistance against large strains and may thereby protect the structuralintegrity of cells.

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