Cellular elasticity drives the mechano-adaptation against fluid shear stress.

Abstract

Cancer cells adapt to external biophysical cues but how the cytoskeletal remodeling facilitate this mechano-adaptation is largely unexplored. Here, we demonstrate that the intrinsic non-muscle myosinII (NMII) activity and self-organization in cancer cells regulate the cellular elastic property 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 NMIIs by siRNA, (-) blebbistatin or Y27632 impairs the stack formation and perturbs cellular elasticity. Moreover, NMII-mediated elasticity regulates cyto-nuclear coupling through its association with LINC complex protein, Nesprin-2, and regulates nuclear import of the mechanoresponsive proteins, YAP/TAZ, 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.