title: Lipid membranes with a majority of cholesterol: applications to the ocular lens and aquaporin 0.
abstract: Using molecular dynamics (MD) simulations, we studied the structure and dynamics of two dimyristoylphosphatidylcholine (DMPC):cholesterol bilayers at concentrations representative of the ocular lens (ratios of 1:1 and 1:2). These MD simulations agree well with experimental deuterium order parameters and bilayer peak-to-peak distances. Although it is known that the average surface area per lipid rapidly decreases from low to moderate levels of cholesterol, our simulations indicate that there is a relatively small change in the average lipid area from 50 to 66.7% cholesterol (40.5 ± 0.2 and 39.5 ± 0.1 Å(2)/lipid, respectively). Radial distribution functions for the hydroxyl group on cholesterol indicate the formation of cholesterol-only nanoscale domains for the membrane with 66.7% cholesterol but a uniform distribution of cholesterol and DMPC for the membrane with 50% cholesterol. These small domains form a single shell of hexagonally packed cholesterols that are interconnected in a web-like structure of cholesterol. Calculations of internal DMPC dynamics show that the relaxation times for carbon-hydrogen reorientation of choline decrease with an increase in cholesterol, but the main body (carbonyl-glycerol to C11) is independent of cholesterol concentration. MD simulations of the aquaporin 0 tetramer show stabilization in its interactions with lipid membranes containing cholesterol by forming ring-ring stacking between surface aromatic residues of the protein and the rings of cholesterol. Moreover, there is an increase in hydrogen bonds with longer lifetimes in a mixed bilayer of DMPC and cholesterol.
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Maryland, College Park, Maryland 20742, United States.
authors.forename: Joseph W
authors.initials: JW
authors.lastname: O'Connor
authors.forename: Jeffery B
authors.initials: JB
authors.lastname: Klauda
mesh_terms: D000818:Animals; D020346:Aquaporins / Q000737:chemistry* / Q000378:metabolism; D002417:Cattle; D002784:Cholesterol / Q000737:chemistry* / Q000378:metabolism; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry* / Q000378:metabolism; D005136:Eye Proteins / Q000737:chemistry* / Q000378:metabolism; D007908:Lens, Crystalline / Q000737:chemistry* / Q000378:metabolism; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D055503:Protein Multimerization
chemical_list: D020346:Aquaporins; D005136:Eye Proteins; D008051:Lipid Bilayers; C030328:aquaporin 0; D002784:Cholesterol; D004134:Dimyristoylphosphatidylcholine