内皮細胞における膜脂質相転移を介したメカノセンシング

抄録

Vascular endothelial cells (ECs) respond to the hemodynamic forces shear stress and stretch by altering their morphology, functions, and gene expression. Here we report that plasma membranes differentiate between stretch and shear stress by undergoing transitions in its lipid phases. Shear stress decreased the lipid order of EC plasma membranes; uniaxial stretching and hypotonic swelling increased the membrane lipid order. Similar changes in lipid order occurred in the artificial lipid bilayer membranes of giant unilamellar vesicles, indicating that these are physical phenomena. Blocking these changes in the membrane lipid order by depleting membrane cholesterol with methyl-β-cyclodextrin or by adding cholesterol resulted in marked inhibitions of the stretch or shear stress induced phosphorylation of PDGF receptors or VEGF receptors, respectively. These results indicate that EC membranes differently respond to hemodynamic forces and that the changes in membrane physical properties are involved in the mechanotransduction that activates membrane receptors to each force.