Cholesterol Protects the Oxidized Lipid Bilayer from Water Injury: An All-Atom Molecular Dynamics Study
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In an effort to delineate how cholesterol protects membrane structure under oxidative stress conditions, we monitored the changes to the structure of lipid bilayers comprising 30 mol% cholesterol and an increasing concentration of Class B oxidized 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) glycerophospholipids, namely, 1-palmitoyl-2-(9′-oxo-nonanoyl)-sn-glycero-3-phosphocholine (PoxnoPC), and 1-palmitoyl-2-azelaoyl-sn-glycero-3-phosphocholine (PazePC), using atomistic molecular dynamics simulations. Increasing the content of oxidized phospholipids (oxPLs) from 0 to 60 mol% oxPL resulted in a characteristic reduction in bilayer thickness and increase in area per lipid, thereby increasing the exposure of the membrane hydrophobic region to water. However, cholesterol was observed to help reduce water injury by moving into the bilayer core and forming more hydrogen bonds with the oxPLs. Cholesterol also resists altering its tilt angle, helping to maintain membrane integrity. Water that enters the 1-nm-thick core region remains part of the bulk water on either side of the bilayer, with relatively few water molecules able to traverse through the bilayer. In cholesterol-rich membranes, the bilayer does not form pores at concentrations of 60 mol% oxPL as was shown in previous simulations in the absence of cholesterol.
KeywordsLipid oxidation Cholesterol protection Oxidative stress Oxidized membranes Pore formation
M. O. thanks the Helmholtz Postdoc Programme. I.V. thanks the European Research Council [Advanced Grant CROWDED-PRO-LIPIDS (Grant No. 290974)]. B.S. thanks the Deutsche Forschungsgemeinschaft for financial support through the Collaborative Research Center SFB 1208 (“Identity and Dynamics of Membrane Systems—from Molecules to Cellular Functions,” Düsseldorf, project A07). The CSC—IT Centre for Science (Espoo, Finland) is acknowledged for excellent computational resources (Project Number tty3995). We also acknowledge grants of computer capacity from the Finnish Grid and Cloud Infrastructure (persistent identifier urn:nbn:fi:research-infras-201).
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Conflict of interests
The authors declare that they have no conflict of interests.
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