Polyunsaturated fatty acids and the effect of phospholipid headgroup on lipid rafts

Omega-3 polyunsaturated fatty acids (n-3 PUFA) are commonly consumed in fish oil supplements for a variety of associated health benefits. Here we investigate the premise that there is an underlying mechanism by which n-3 PUFA incorporated into membrane phospholipids regulate the architecture and functionality of lipid rafts. We ran coarse-grained (CG) MD simulations on lipid mixtures comprised in 1:1:1 mol ratio of palmitoyl sphingomyelin (PSM) and cholesterol with 1-palmitoyl-2-docosahexaenoylphosphatidylcholine (PDPC) or 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) and with 1-palmitoyl-2-docoshexaenoylphosphatidylethanolamine (PDPE) or 1-palmitoyl-oleoylphosphatidylethanolamine (POPE). PSM and cholesterol are raft forming lipids that pack together tightly. PDPC and PDPE, which have polyunsaturated docosahexaenoic acid (DHA) at the sn-2 position, prefer a disordered non-raft environment. After 18 µs of simulation, visual inspection confirms that PSM and cholesterol cluster together more in the presence of PDPC than POPC. We attribute the increase in clustering to the greater difference in order parameter measured for the polyunsaturated phospholipid relative to PSM. The clustering of PSM and cholesterol appears less for PDPE and POPE, reflecting a smaller differential in order between PE and PSM that we ascribe to the smaller headgroup of PE and resulting intrinsically higher order.