Cholesterol Modulated Interdigitation Of Long-Chain Sphingomyelin And Glycolipids

Long-chain sphingomyelin (SM) and glycolipids are not among the most abundant species of lipids, however they can be enriched in specific cells or organelles. For example, lipidomics data determined for exosomes released by PC-3 prostate cancer cells showed that exosomes are particularly enriched in long-chain SM (Biochim. Biophys.Acta, 2013, 1831, 1302–1309). In this study, we use atomistic molecular dynamics simulations to consider asymmetric lipid membrane models whose compositions are based on these data. The simulations show interdigitation of the long-chain SM to the opposite leaflet, which is quite expected, but interestingly we found out that interdigitation was particularly strong in asymmetric bilayers compared to symmetric ones. We observed that the conformational order of the amide-linked SM chain increases the deeper it penetrates to the opposing leaflet. We further showed that cholesterol modulates the effect of SM interdigitation by influencing the conformational order of lipid hydrocarbon chains in the opposing (cytosolic) leaflet.