title: 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.
abstract: Vascular endothelium transduces the temporal gradients in shear stress (tau) originating from unsteady blood flow into functional responses. We measured the effects of step-tau and ramp-tau (i.e., t 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-tau 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-tau 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-tau but not by ramping to the same tau 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 tau with spatial discrimination and that the tau-induced membrane perturbations can be transduced into MAPK activation. These results have implications for understanding the role of t in modulating vascular functions in health and disease.
authors.affiliation: Department of Bioengineering and The Whitaker Institute of Biomedical Engineering, University of California, San Diego, La Jolla, California 92093, USA. pjbbio@engr.psu.edu
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Butler
authors.forename: Tsui-Chun
authors.initials: TC
authors.lastname: Tsou
authors.forename: Julie Yi-Shuan
authors.initials: JY
authors.lastname: Li
authors.forename: Shunichi
authors.initials: S
authors.lastname: Usami
authors.forename: Shu
authors.initials: S
authors.lastname: Chien
mesh_terms: D019905:Benzyl Alcohol / Q000494:pharmacology; D002784:Cholesterol / Q000494:pharmacology; D004058:Diffusion; D004730:Endothelium, Vascular / Q000737:chemistry* / Q000166:cytology / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects; D048031:JNK Mitogen-Activated Protein Kinases; D008051:Lipid Bilayers / Q000737:chemistry; D048670:MAP Kinase Kinase 4; D008560:Membrane Fluidity / Q000187:drug effects; D008563:Membrane Lipids / Q000737:chemistry*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D012680:Sensitivity and Specificity; D013314:Stress, Mechanical
chemical_list: D008051:Lipid Bilayers; D008563:Membrane Lipids; D002784:Cholesterol; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; D019905:Benzyl Alcohol