Sphingomyelin analogues with differently branched N-acyl chains: effect on acyl chain order and sterol interaction in bilayer membranes

Sphingolipids have been found to have single methyl branchings both in their long-chain base as well as in their N-linked acyl chains. In this study we determined how methyl-branching in N-linked acyl chain of sphingomyelins affect their membrane properties. SM analog with a single methyl branching at carbon 15 (of a 17:0 acyl chain; anteiso) had a lower gel-liquid transition temperature as compared with an isobranched SM analog. Phytanoyl SM (methyls at carbons 3, 7, 11 and 15) as well as a SM analog with a methyl on carbon 10 in a hexadecanoyl chain failed to show a gel-liquid transition above 10 °C. Only the two distally branched SM analogs (iso and anteiso) formed ordered domains with cholesterol in a 1-palmitoyl-2-oleoyl phosphatidylcholine (POPC) bilayer. However, domains formed by the branched SM analogs appeared to contain less sterol when compared to palmitoyl SM (PSM) as the saturated phospholipid. Sterol-enriched domains formed by the anteiso SM analog were also less stable against temperature than domains formed by PSM. Both the 10-methyl and phytanoyl SM analogs failed to form sterol-enriched domains in the POPC bilayer. Acyl chain branching weakened SM/sterol interaction markedly when compared to PSM, as evidenced from the decreased affinity of cholestatrienol to bilayers containing branched SM analogs. Our results show that methyl branching weakened intermolecular interactions in a position-dependent manner.