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Asymmetric structural features in single supported lipid bilayers containing cholesterol and GM1 resolved with synchrotron X-Ray reflectivity.

ABSTRACT: The cell membrane comprises numerous protein and lipid molecules capable of asymmetric organization between leaflets and liquid-liquid phase separation. We use single supported lipid bilayers (SLBs) to model cell membranes, and study how cholesterol and asymmetrically oriented ganglioside receptor G(M1) affect membrane structure using synchrotron x-ray reflectivity. Using mixtures of cholesterol, sphingomyelin, and 1,2-dioleoyl-sn-glycero-3-phosphocholine, we characterize the structure of liquid-ordered and liquid-disordered SLBs in terms of acyl-chain density, headgroup size, and leaflet thickness. SLBs modeling the liquid-ordered phase are 10 A thicker and have a higher acyl-chain electron density (rho(chain) = 0.33 e(-)/A(3)) compared to SLBs modeling the liquid-disordered phase, or pure phosphatidylcholine SLBs (rho(chain) = 0.28 e(-)/A(3)). Incorporating G(M1) into the distal bilayer leaflet results in membrane asymmetry and thickening of the leaflet of 4-9 A. The structural effect of G(M1) is more complex in SLBs of cholesterol/sphingomyelin/1,2-dioleoyl-sn-glycero-3-phosphocholine, where the distal chains show a high electron density (rho(chain) = 0.33 e(-)/A(3)) and the lipid diffusion constant is reduced by approximately 50%, as measured by fluorescence microscopy. These results give quantitative information about the leaflet asymmetry and electron density changes induced by receptor molecules that penetrate a single lipid bilayer.

SUBMITTER: Reich C

PROVIDER: S-EPMC2440463 | biostudies-literature | 2008 Jul

REPOSITORIES: biostudies-literature

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Asymmetric structural features in single supported lipid bilayers containing cholesterol and GM1 resolved with synchrotron X-Ray reflectivity.

Reich Christian C Horton Margaret R MR Krause Bärbel B Gast Alice P AP Rädler Joachim O JO Nickel Bert B

Biophysical journal 20080328 2

The cell membrane comprises numerous protein and lipid molecules capable of asymmetric organization between leaflets and liquid-liquid phase separation. We use single supported lipid bilayers (SLBs) to model cell membranes, and study how cholesterol and asymmetrically oriented ganglioside receptor G(M1) affect membrane structure using synchrotron x-ray reflectivity. Using mixtures of cholesterol, sphingomyelin, and 1,2-dioleoyl-sn-glycero-3-phosphocholine, we characterize the structure of liquid ...[more]

PMID: 18375517

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Project description:Cholesterol trafficking, which is an essential function in mammalian cells, is intimately connected to molecular-scale interactions through cholesterol modulation of membrane structure and dynamics and interaction with membrane receptors. Since these effects of cholesterol occur on micro- to millisecond timescales, it is essential to develop accurate coarse-grained simulation models that can reach these timescales. Cholesterol has been shown experimentally to thicken the membrane and increase phospholipid tail order between 0-40% cholesterol, above which these effects plateau or slightly decrease. Here, we showed that the published MARTINI coarse-grained force-field for phospholipid (POPC) and cholesterol fails to capture these effects. Using reference atomistic simulations, we systematically modified POPC and cholesterol bonded parameters in MARTINI to improve its performance. We showed that the corrections to pseudo-bond angles between glycerol and the lipid tails and around the oleoyl double bond particle (the "angle-corrected model") slightly improves the agreement of MARTINI with experimentally measured thermal, elastic, and dynamic properties of POPC membranes. The angle-corrected model improves prediction of the thickening and ordering effects up to 40% cholesterol but overestimates these effects at higher cholesterol concentration. In accordance with prior work that showed the cholesterol rough face methyl groups are important for limiting cholesterol self-association, we revised the coarse-grained representation of these methyl groups to better match cholesterol-cholesterol radial distribution functions from atomistic simulations. In addition, by using a finer-grained representation of the branched cholesterol tail than MARTINI, we improved predictions of lipid tail order and bilayer thickness across a wide range of concentrations. Finally, transferability testing shows that a model incorporating our revised parameters into DOPC outperforms other CG models in a DOPC/cholesterol simulation series, which further argues for its efficacy and generalizability. These results argue for the importance of systematic optimization for coarse-graining biologically important molecules like cholesterol with complicated molecular structure.

Dataset Information

Asymmetric structural features in single supported lipid bilayers containing cholesterol and GM1 resolved with synchrotron X-Ray reflectivity.

Publications

Asymmetric structural features in single supported lipid bilayers containing cholesterol and GM1 resolved with synchrotron X-Ray reflectivity.

Similar Datasets

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