Vimentin Promotes Collective Migration and Invasion Under Compressive Stress in 3D Spheroids

Vimentin is an intermediate filament protein that is known for protecting the mechanical integrity of cells at large strains, but its effects on the mechanics of collections of cells remain unclear. In this study, we generated wild-type and vimentin-null mouse embryonic fibroblast (MEF) spheroids embedded in 3D collagen matrix under compressive load to investigate the role of vimentin in collective behavior under compression. We observed that wild-type spheroids display higher cellular dynamics and invasiveness under compression, while the vimentin-null spheroids show little change. We show using 3D nuclear shape data and 3D vertex simulations that wild-type spheroids are more fluid-like compared to the vimentin-null spheroids. Our experimental results are consistent with our 3D vertex simulation, which shows that the effect of compression-induced fluidization is more pronounced on fluid-like spheroids (wild-type) than on solid-like spheroids (vimentin-null). Altogether, these changes suggest that vimentin promotes collective migration in response to compressive stress.