Cell migration is a critical process underlying proper tissue maintenance. While a soft nucleus allows a cell to squeeze through small pores, the resulting physical stress can lead to nuclear damage and genomic variability. We have shown that the cytoskeletal intermediate filament protein vimentin protects against DNA damage during migration. We present a mechanical model in which vimentin modulates force transmission and nuclear deformability, which becomes especially evident under conditions of extreme, yet physiologically-relevant cellular deformations. Finally, new results will be presented on how vimentin mediates intracellular microtubule dynamics and extracellular matrix remodeling to facility cell motility.