Cellular elasticity drives mechano-adaptation against fluid shear stress

Cancer cells adapt to external biophysical cues, but how cytoskeletal remodeling facilitates this mechano-adaptation is largely unexplored. Here, we demonstrate that intrinsic non-muscle myosin II (NMII) activity and self-organization in cancer cells regulate cellular elastic properties when cells are exposed to fluid shear stress (FSS). In association with the reorganized actin filament network, NMII bipolar filaments can assemble into aligned stacks, which allow cellular stretching upon exposure to FSS. Inhibition of NMII by treatment with small interfering RNA, (-)blebbistatin or Y27632 impairs the stack formation and perturbs cellular elasticity. Moreover, NMII-mediated elasticity regulates cyto-nuclear coupling through its association with the LINC complex protein nesprin2 and regulates nuclear import of the mechanoresponsive proteins YAP1 and TAZ (also known as WWTR1), which induce differential expression of genes thus decreasing growth and migration in FSS-exposed cells. These findings reveal that the cellular elasticity mediated by NMII dynamics provides mechano-adaptation against a mechanical stress, like FSS.