Vimentin intermediate filament networks are required for compression stiffening of cells and protection of nuclei from compressive stress.

The semi-flexible polymer networks that form the cytoskeleton are heterogeneously distributed and are regulated by different molecular mechanisms. In mesenchymal cells, the intermediate filament network formed by vimentin is concentrated near the nucleus, although it also makes some contacts with the actin-rich cell cortex.  The physical properties of the three cytoskeletal filaments and the networks they form are also distinct, especially in uniaxial deformation.  Rigid and semi-flexible biopolymer networks generally stiffen when deformed in shear but soften in compression due to filament buckling.   However, unlike crosslinked networks of purified F-actin or microtubules, which soften in compression, vimentin intermediate filament networks stiffen in both compression and extension by a mechanism that involves the greater flexibility of vimentin and the large surface charge of the vimentin filament that resists volume changes under compression. Individual cells, such as fibroblasts, stiffen at physiologically relevant compressive strains, but deletion of vimentin diminishes this effect. Vimentin null fibroblasts suffer greater damage to the nucleus after cell compression than normal cells. These results provide a new framework by which to understand the mechanical responses of cells and point to a central role of intermediate filaments in response to compression