Cytoskeletal reorganization in endothelial cells subjected to shear stress and circumferential stretch simultaneously

Hemodynamic forces affect the morphology and function of endothelial cells (EC) lining the arteries, and are implicated in the localization and development of various cardiovascular diseases. EC and their cellular scaffolding, the actin cytoskeleton, align and reorganize under the effect of these mechanical forces. Until recently most in vitro studies have focused on the isolated effects of shear stress or circumferential strain on the morphology and cytoskeletal organization of EC. Recent experimental investigations of the exposure of EC to both forces revealed a synergistic aspect of the phenomenon. It was found that, simultaneous exposure of EC to both shear and strain near the threshold levels for alignment (>2 dynes/cm² or >2, respectively) resulted in enhanced morphological change and cytoskeletal alignment. Based on two previous models accounting for the isolated effects of these forces, the authors develop a model where the cortical cytoskeletal filaments are exposed to both shear and stretch at the apical and basal surfaces, respectively, and interact with other cytoskeletal filaments. The model shows that coupling of filaments connected with the membrane and other cytoskeletal filaments through dynamic biochemical interactions together with the proposed mechanotransmission mechanism is sufficient to account for the observed enhanced effect of alignment