The Journal of Membrane Biology

, Volume 251, Issue 3, pp 521–534 | Cite as

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
Part of the following topical collections:
  1. Lipid Membranes and Reactions at Lipid Interfaces: Theory, experiments, and applications


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.


Lipid 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).

Compliance with Ethical Standards

Conflict of interests

The authors declare that they have no conflict of interests.

Supplementary material

232_2018_28_MOESM1_ESM.pdf (835 kb)
Supplementary material 1 (PDF 835 KB)


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Institute of Complex Systems: Structural Biochemistry (ICS-6)Forschungszentrum JülichJülichGermany
  2. 2.CEITEC – Central European Institute of TechnologyMasaryk UniversityBrnoCzech Republic
  3. 3.Department of PhysicsUniversity of HelsinkiHelsinkiFinland
  4. 4.Department of PhysicsTampere University of TechnologyTampereFinland
  5. 5.MEMPHYS - Center for Biomembrane Physics, University of Southern DenmarkOdenseDenmark
  6. 6.Institute of Theoretical and Computational ChemistryHeinrich Heine University DüsseldorfDüsseldorfGermany

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