Cholesterol promotes similar chain packing in n-3 PUFA-containing membranes.

Abstract

Cholesterol's organization in biomembranes has great influence on membrane function. Omega-3 polyunsaturated fatty acid (n-3 PUFA)-containing lipids are believed to have a myriad of health benefits and are known to modulate membrane organization in model membranes via their aversion for cholesterol. 2H NMR has observed that different n-3 PUFA-containing phosphatidylcholine (PC) lipids modulate membrane organization to different degrees. In ternary lipid mixtures with sphingomyelin and cholesterol, docosahexaenoic acid (DHA, 22:6)-containing PC infiltrates lipid rafts more than eicosapentaenoic acid (EPA, 20:5)-containing PC. Additionally, molecular dynamics (MD) simulations have shown that n-3 PUFA-containing membranes differ in their stereospecific interactions with cholesterol. The mean-torque model provides a method of relating lipid disorder to a thermodynamic parameter (potential of mean torque) which can be used to quantify lipid-lipid interactions. Here we apply this approach to compare 1-stearoyl-2-eicosapentaenoylphosphatylcholine (EPA-PC, 18:0-20:5PC), 1-stearoyl-2-docosahexaenoylphosphatylcholine (DHA-PC, 18:0-22:6PC), 1-stearoyl-2-docosapentaenoylphosphatylcholine (DPA-PC, 18:0-22:5PC) and, as a monounsaturated control, 1-stearoyl-2-oleoylphosphatidylcholine (OA-PC, 18:0-18:1PC) bilayers and their interactions with cholesterol. Analysis of data from 2H NMR and MD simulations shows that all three n-3 PUFA-containing phospholipids display similar chain packing in the presence of cholesterol, which is illustrated by the projected chain length of the sn-1 chains.