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Lipid Membranes with a Majority of Cholesterol: Applications to the Ocular Lens and Aquaporin 0.
MedLine Citation:
PMID:  21539340     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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:
Joseph W O'Connor; Jeffery B Klauda
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-5-3
Journal Detail:
Title:  The journal of physical chemistry. B     Volume:  -     ISSN:  1520-5207     ISO Abbreviation:  -     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-5-4     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101157530     Medline TA:  J Phys Chem B     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Chemical and Biomolecular Engineering, University of Maryland , College Park, Maryland 20742, United States.
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