Cholesterol Protects the Oxidized Lipid Bilayer from Water Injury: An All-Atom Molecular Dynamics Study

Michael C. Owen, Waldemar Kulig, Tomasz Rog, Ilpo Vattulainen, Birgit Strodel

    Research output: Contribution to journalArticleScientificpeer-review

    8 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)521-534
    Number of pages14
    JournalJournal of Membrane Biology
    Volume251
    Issue number3
    Early online date17 Mar 2018
    DOIs
    Publication statusPublished - Jun 2018
    Publication typeA1 Journal article-refereed

    Keywords

    • Cholesterol protection
    • Lipid oxidation
    • Oxidative stress
    • Oxidized membranes
    • Pore formation

    Publication forum classification

    • Publication forum level 1

    ASJC Scopus subject areas

    • Biophysics
    • Physiology
    • Cell Biology

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