Regulation of endothelial cell migration by amphiphiles - are changes in cell membrane physical properties involved?
Endothelial cell (EC) migration is an integral part of angiogenesis and a prerequisite for malignant tumor growth. Recent studies suggest that amphiphilic compounds can regulate migration of bovine aortic ECs by altering the physical properties of the cell membrane lipid bilayers. A number of structurally different amphiphiles thus regulate the migration in quantitative correlation with their effects on the plasma membrane microviscosity. Many amphiphiles that affect EC migration and angiogenesis alter the physical properties of lipid bilayers, suggesting that such a regulatory mechanism may be of general importance. To investigate this notion, we studied the effects of lysophospholipids that inhibit migration of bovine aortic ECs and decrease cell membrane microviscosity, and of other amphiphiles that decrease membrane microviscosity (Triton X-100, octyl-beta-glucoside, arachidonic acid, docosahexaenoic acid, ETYA, capsaicin) on the migration of porcine aortic ECs. We further studied whether the enzyme secretory phospholipase A(2) (sPLA(2)) would affect migration in accordance with the changes in membrane microviscosity induced by its hydrolysis products lysophospholipids and polyunsaturated fatty acids. Arachidonic acid, at low concentrations, promoted cell migration by a mechanism involving metabolic products of this compound. Apart from this effect, all the amphiphiles, as well as sPLA(2), inhibited cell migration. A semi-quantitative analysis found a similar correlation between the effects on migration and on lipid bilayer stiffness measured using gramicidin channels as molecular force transducers. These results suggest that changes in cell membrane physical properties may generally contribute to the effects of amphiphiles on EC migration.
Jensen
Lasse D E
LD
Department of Cancer and Immunobiology, Novo Nordisk A/S, Novo Nordisk Park, Måløv, Denmark.
Hansen
Anker J
AJ
Lundbaek
Jens A
JA
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D018929:Cell Culture Techniques / Q000379:methods; D002462:Cell Membrane / Q000187:drug effects* / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology*; D004281:Docosahexaenoic Acids / Q000378:metabolism; D042783:Endothelial Cells / Q000502:physiology*; D005960:Glucosides / Q000737:chemistry / Q000494:pharmacology; D008051:Lipid Bilayers / Q000737:chemistry; D008246:Lysophospholipids / Q000378:metabolism; D008560:Membrane Fluidity / Q000187:drug effects* / Q000502:physiology; D008563:Membrane Lipids / Q000378:metabolism; D017830:Octoxynol / Q000737:chemistry / Q000494:pharmacology; D013501:Surface-Active Agents / Q000737:chemistry / Q000494:pharmacology*; D013552:Swine
D005960:Glucosides; D008051:Lipid Bilayers; D008246:Lysophospholipids; D008563:Membrane Lipids; D013501:Surface-Active Agents; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; C018619:octyl-beta-D-glucoside; D017830:Octoxynol