Effect of Combined Cyclic Stretch and Fluid Shear Stress on Endothelial Cell Morphological Responses

Abstract

Endothelial cells in vivo are normally subjected to multiple mechanical stimuli such as stretch and fluid shear stress (FSS) but because each stimulus induces magnitude-dependent morphologic responses, the relative importance of each stimulus in producing the normal in vivo state is not clear Using cultured human aortic endothelial cells, this study first determined equipotent levels of cyclic stretch, steady FSS, and oscillatory FSS with respect to the time course of cell orientation. We then tested whether these levels of stimuli were equipotent in combination with each other by imposing simultaneous cyclic stretch and steady FSS or cyclic stretch and oscillatory FSS so as to reinforce or counteract the cells' orientation responses. Equipotent levels of the three stimuli were 2% cyclic stretch at 2%/s, 80 dynes/cm2 steady FSS and 20 +/- 10 dynes/cm2 oscillatory FSS at 20 dyne/cm2-s. When applied in reinforcing fashion, cyclic stretch and oscillatory, but not steady, FSS were additive. Both pairs of stimuli canceled when applied in counteracting fashion. These results indicate that this level of cyclic stretch and oscillatory FSS sum algebraically so that they are indeed equipotent. In addition, oscillatory FSS is a stronger stimulus than steady FSS for inducing cell orientation. Moreover, arterial endothelial cells in vivo are likely receiving a stronger stretch than FSS stimulus.

Single membrane tether extraction from adult and neonatal dermal microvascular endothelial cells

“…However, endothelial cells in vivo are constantly subjected to blood flow and shear stress, which may affect their morphological and mechanical properties (17,22,23). Therefore, it is essential to investigate tether extraction from endothelial cells exposed to shear stress.…”

Multi-scale interaction of particulate flow and the artery wall

“…Phenomenologically, this coupling (of EC morphology with WSS) manifests itself in increasing WSS with changes in EC conformation (6): in vitro, ECs elongate, changing from a polygonal, 'cobblestone' morphology to flattened, elongated ovoids (Figures 2a, 2b), the degree of elongation correlating with the magnitude of the shear stress (7)(8)(9)(10). Note that WSS type, too, is relevant-under oscillatory shear, cultured cells retain a polygonal shape (8) and in vivo, ECs have been shown to orientate to the predominant local flow direction (11), perpendicular to the direction of cyclic stretch (12,13). Such observed behavior -4 -should, of course, emerge from a correct and self-consistent model coupling the endothelial state with flow.…”

Fluid dynamic analysis of flow in orbiting dishes and the effects of flow on shear stress and endothelial cellular responses.

“…Owatverot, et at. (25) found that unidirectional pulsatile shear stress on cultured human aortic endothelial cells was a stronger stimulus than steady shear for inducing cell orientation. It was observed that pure uniaxial cyclic strain of 2% at 0.…”