Vimentin intermediate filaments increases collective cell migration through extracellular matrix networks

The intermediate filament protein vimentin 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 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. Traction force analysis reveals that vimentin null spheroids exert less contractile force than their wild-type counterparts. In addition, we show that vimentin-containing fibroblasts increase the invasiveness of MDA-MB-231 co-culture spheroids compared to vimentin-null fibroblasts. Altogether, these results signify that vimentin plays a critical role in enhancing migratory persistence in 3D environments, a hallmark feature of diseases such as fibrosis and cancer.