Effect of lipid peroxidation on the properties of lipid
bilayers: a molecular dynamics study
Jirasak Wong-ekkabut 1, Zhitao Xu 2, Wannapong Triampo 1, I-Ming Tang 1, Peter Tieleman 3 and Luca Monticelli 3*
1 Mahidol University
2 California Institute of Technology
3 University of Calgary
* To whom correspondence should be addressed. E-mail: luca.monticelli{at}ucalgary.ca.
Submitted on May 11, 2007
Revised on June 14, 2007
Accepted on 5 July 2007
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Abstract |
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Lipid peroxidation plays an important role in cell membrane damage. We investigated the effect of lipid peroxidation on the properties of 1-palmitoyl-2-linoleoyl-sn-glycero-3-phosphatidylcholine (PLPC) lipid bilayers using molecular dynamics simulations. We focused on four main oxidation products of linoleic acid with either a hydroperoxide or an aldehyde group: 9-trans, cis-hydroperoxide linoleic acid, 13-trans, cis-hydroperoxide linoleic acid, 9-oxononanoic acid, and 12-oxo-9-dodecadienoic acid. These oxidized chains replaced the sn-2 linoleate chain. The properties of PLPC lipid bilayers were characterized as a function of the concentration of oxidized lipids, with concentrations from 2.8% to 50% for each oxidation product. The introduction of oxidized functional groups in the lipid tail leads to an important conformational change in the lipids: the oxidized tails bend towards the water phase and the oxygen atoms form hydrogen bonds with water and the polar lipid head group. This conformational change leads to an increase in the average area per lipid and, correspondingly, to a decrease of the bilayer thickness and the deuterium order parameters for the lipid tails, especially evident at high concentrations of oxidized lipid. Water defects are observed in the bilayers more frequently as the concentration of the oxidized lipids is increased. The changes in the structural properties of the bilayer and the water permeability are associated with the tendency of the oxidized lipid tails to bend towards the water interface. Our results suggest that one mechanism of cell membrane damage is the increase in membrane permeability due to the presence of oxidized lipids.
Key Words:
bilayer structure, computer simulation, lipid peroxidation, membrane damage, membrane permeability, water defect
