Long chain sphingomyelin depletes cholesterol from the cytoplasmic leaflet in asymmetric lipid membranes. Issue 37 (28th June 2021)

• Record Type: Journal Article
• Authors: Karlsen, Maria Lyngby; Bruhn, Dennis S.; Pezeshkian, Weria; Khandelia, Himanshu
• Is Part Of: RSC advances. Volume 11:Issue 37(2021)
• Page Start: 22677
• Page End: 22682
• Publication Date: 2021-06-28
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/d1ra01464a
• Languages: English
• ISSNs: 2046-2069

Abstract

Abstract : Long acyl chain sphingomyelin and saturated phospholipid tails in the outer membrane leaflet deplete cholesterol from the inner leaflet in mammalian membranes. Abstract : The transbilayer distribution of cholesterol (CHL) in complex asymmetric lipid membranes remains controversial, with contrasting investigations suggesting that there is more CHL either in the exoplasmic, outer leaflet (OL) or the cytoplasmic, inner leaflet (IL) depending on cell type or model, membrane composition, and method of investigation. Here, we launch systematic coarse-grained molecular dynamics simulations to investigate the impact of the sphingomyelin (SM) acyl chain length upon CHL distribution in asymmetric lipid membrane mixtures which account for the variation of the most abundant headgroups and acyl chain unsaturation in the two membrane leaflets. We find that there is always more CHL in the OL, but longer chain SM depletes more CHL from the IL than short chain SM in simple membrane mixtures containing SM and 16 : 0, 18 : 1 phospholipids. The difference between longer and shorter chain SM is neutralised in a more complex asymmetric membrane, where there are more saturated tails in the outer leaflet. We propose that interdigitation of long-chain SM into the opposing IL pushes cytoplasmic CHL towards the OL, but higher chain saturation of the outer leaflet compensates for the effect of SM chain length.