Vimentin intermediate filaments increases collective cell migration through extracellular matrix network

The intermediate filament (IF) protein vimentin (V) is associated with many diseases with phenotypes of enhanced cellular migration and aggressive invasion through the extracellular matrix (ECM) of tissues, but vimentin's role in in vivo cell migration is still largely unclear. Vimentin is important for proper cellular adhesion and force generation, which are critical to cell migration; yet, the vimentin cytoskeleton also hinders the ability of cells to squeeze through small pores in ECM, resisting migration. To identify the role of vimentin in collective cell migration, we generate spheroids of wide-type and vimentin-null mouse embryonic fibroblast (mEF) and embed them in a 3D collagen matrix. We find that loss of vimentin significantly impairs the ability of the spheroid to collectively expand through collagen networks and remodel the collagen network. In addition, coculture of vimentin-null and wild-type mEFs leads to a persistent sorting pattern: wild-type cells enveloping vimentin-null cells, suggesting differential adhesion between these two cell lines. Taken together, these results signify that VIF play a critical role in enhancing migratory persistence in 3D environments, a hallmark feature of diseases such as fibrosis and cancer.