Vimentin supports directional cell migration by controlling focal adhesions

AbstractFibroblastic migration is of key importance in wound healing. While the intermediate filament (IF) protein vimentin is required for normal wound healing, we examined whether vimentin-mediated regulation of fibroblast migration could be involved. In wound healing assays triggering cell polarization and directed migration, we observed that vimentin-deficient mouse and rat embryonic fibroblasts lost their directional persistence. We show that vimentin maintains directionality by guiding focal adhesions (FAs) in fibroblasts. Detailed analysis showed that vimentin stabilizes FAs and regulates their disassembly rate. The destabilization of Vim-/- FAs was reflected by smaller FAs. Live cell and super-resolution imaging demonstrate that vimentin interacts dynamically with the key molecules of FAs and, importantly, with FAK, which is crucial for the maturation of FAs. These results demonstrate that vimentin IFs control the maturation, stability, dynamics, arrangement, and overall orientation of FAs, with a net effect on FA coordination during migration.