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Rate sensitivity of shear‐induced changes in the lateral diffusion of endothelial cell membrane lipids: a role for membrane perturbation in shear‐induced MAPK activation

Vascular endothelium transduces the temporal gradients in shear stress (τ) originating from unsteady blood flow into functional responses. We measured the effects of step‐τ and ramp‐τ (i.e., τ with different temporal shear gradients) on the lipid lateral diffusion coefficient (D) in the apical membranes of confluent cultured bovine aortic endothelial cells by using fluorescence recovery after photobleaching. A step‐τ of 10 dynes/cm2 elicited a rapid (5 s) increase of D in the portion of the cell upstream of the nucleus and a concomitant decrease in the downstream portion. A ramp‐τ with a rate of 20 dynes/cm2 per min elicited a rapid (5 s) decrease of D in both the upstream and the downstream portions. The mitogen‐activated protein kinases (MAPKs) ERK and JNK were activated by step‐τ but not by ramping to the same τ level. Benzyl alcohol, which increases D, enhanced the activities of both MAPKs; cholesterol, which reduces D, diminished these activities. We conclude that the lipid bilayer can sense the temporal features of the applied τ with spatial discrimination and that the τ‐induced membrane perturbations can be transduced into MAPK activation. These results have implications for understanding the role of τ in modulating vascular functions in health and disease.