title: Cholesterol effects on the phosphatidylcholine bilayer polar region: a molecular simulation study.
abstract: A molecular dynamics (MD) simulation of a fully hydrated, liquid-crystalline dimyristoylphosphatidylcholine (DMPC)-Chol bilayer membrane containing approximately 22 mol% Chol was carried out for 4.3 ns. The bilayer reached thermal equilibrium after 2.3 ns of MD simulation. A 2.0-ns trajectory generated during 2.3-4.3 ns of MD simulation was used for analyses to determine the effects of Chol on the membrane/water interfacial region. In this region, 70% of Chol molecules are linked to DMPC molecules via short-distance interactions, where the Chol hydroxyl group (OH-Chol) is 1) charge paired to methyl groups of the DMPC choline moiety ( approximately 34%), via the hydroxyl oxygen atom (Och); 2) water bridged to carbonyl ( approximately 19%) and nonester phosphate ( approximately 14%) oxygen atoms, via both Och and the hydroxyl hydrogen atom (Hch); and 3) directly hydrogen (H) bonded to carbonyl ( approximately 11%) and nonester phosphate ( approximately 5%) oxygen atoms, via Hch ( approximately 17% of DMPC-Chol links are multiple). DMPC's gamma-chain carbonyl oxygen atom is involved in 44% of water bridges and 51% of direct H bonds formed between DMPC and Chol. On average, a Chol molecule forms 0.9 links with DMPC molecules, while a DMPC molecule forms 2.2 and 0.3 links with DMPC and Chol molecules, respectively. OH-Chol makes hydrogen bonds with 1.1 water molecules, preferentially via Hch. The average number of water molecules H bonded to the DMPC headgroup is increased by 7% in the presence of Chol. These results indicate that inclusion of Chol decreases interlipid links and increases hydration in the polar region of the membrane.
authors.affiliation: Department of Biophysics, Institute of Molecular Biology, Jagiellonian University, Kraków, Poland. mpg@mol.uj.edu.pl
authors.forename: M
authors.initials: M
authors.lastname: Pasenkiewicz-Gierula
authors.forename: T
authors.initials: T
authors.lastname: Róg
authors.forename: K
authors.initials: K
authors.lastname: Kitamura
authors.forename: A
authors.initials: A
authors.lastname: Kusumi
mesh_terms: D002784:Cholesterol / Q000737:chemistry*; D003460:Crystallization; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry*; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry*; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D013997:Time Factors
chemical_list: D008051:Lipid Bilayers; D002784:Cholesterol; D004134:Dimyristoylphosphatidylcholine