title: Membrane microviscosity regulates endothelial cell motility.
abstract: Endothelial cell (EC) movement is an initiating and rate-limiting event in the neogenesis and repair of blood vessels. Here, we explore the hypothesis that microviscosity of the plasma membrane (PM) is a key physiological regulator of cell movement. Aortic ECs treated with membrane-active agents, such as alpha-tocopherol, cholesterol and lysophospholipids, exhibited a biphasic dependency on membrane microviscosity, in which moderate increases enhanced EC migration, but increases beyond a threshold markedly inhibited migration. Surprisingly, angiogenic growth factors, that is, basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), also increased membrane microviscosity, as measured in live cells by fluorescence recovery after photobleaching (FRAP). The localization of Rac to the PM was modified in cells treated with membrane-active agents or growth factors, suggesting a molecular mechanism for how membrane microviscosity influences cell movement. Our data show that angiogenic growth factors, as well as certain lipophilic molecules, regulate cell motility through alterations in membrane properties and the consequent relocalization of critical signalling molecules to membranes.
authors.affiliation: Department of Cell Biology, The Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
authors.forename: Prabar K
authors.initials: PK
authors.lastname: Ghosh
authors.forename: Amit
authors.initials: A
authors.lastname: Vasanji
authors.forename: Gurunathan
authors.initials: G
authors.lastname: Murugesan
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Eppell
authors.forename: Linda M
authors.initials: LM
authors.lastname: Graham
authors.forename: Paul L
authors.initials: PL
authors.lastname: Fox
mesh_terms: D000818:Animals; D016880:Anisotropy; D001011:Aorta / Q000166:cytology*; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism*; D002465:Cell Movement; D002478:Cells, Cultured; D002784:Cholesterol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D007150:Immunohistochemistry; D008246:Lysophospholipids / Q000494:pharmacology; D008833:Microcirculation; D008856:Microscopy, Fluorescence; D038761:Photobleaching; D015398:Signal Transduction; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D024502:alpha-Tocopherol / Q000494:pharmacology
chemical_list: D008246:Lysophospholipids; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D002784:Cholesterol; D024502:alpha-Tocopherol