Long chain sphingomyelin depletes cholesterol from the cytoplasmic leaflet in asymmetric lipid membranes
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Long chain sphingomyelin depletes cholesterol from the cytoplasmic leaflet in asymmetric lipid membranes. / Karlsen, Maria Lyngby; Bruhn, Dennis S.; Pezeshkian, Weria; Khandelia, Himanshu.
In: RSC Advances, Vol. 11, No. 37, 08.07.2021, p. 22677-22682.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Long chain sphingomyelin depletes cholesterol from the cytoplasmic leaflet in asymmetric lipid membranes
AU - Karlsen, Maria Lyngby
AU - Bruhn, Dennis S.
AU - Pezeshkian, Weria
AU - Khandelia, Himanshu
PY - 2021/7/8
Y1 - 2021/7/8
N2 - 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.
AB - 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.
KW - COARSE-GRAINED MODEL
KW - MOLECULAR-DYNAMICS
KW - ORGANIZATION
KW - GROMACS
U2 - 10.1039/d1ra01464a
DO - 10.1039/d1ra01464a
M3 - Journal article
C2 - 35480443
VL - 11
SP - 22677
EP - 22682
JO - RSC Advances
JF - RSC Advances
SN - 2046-2069
IS - 37
ER -
ID: 316749556