This Article Full Text Full Text (PDF) All Versions of this Article: biophysj.107.112565v1 93/12/4225    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Wong-ekkabut, J. Articles by Monticelli, L. Search for Related Content PubMed PubMed Citation Articles by Wong-ekkabut, J. Articles by Monticelli, L.

Effect of Lipid Peroxidation on the Properties of Lipid Bilayers: A Molecular Dynamics Study

Jirasak Wong-ekkabut ^* , Zhitao Xu ^*, Wannapong Triampo  , I-Ming Tang  , D. Peter Tieleman ^* and Luca Monticelli ^*

^* Department of Biological Sciences, University of Calgary, Calgary, Alberta, Canada; and Department of Physics, Mahidol University, Center for Vector and Vector-Borne Diseases, and Center of Nanoscience and Nanotechnology, Mahidol University, Bangkok, Thailand

Correspondence: Address reprint requests to Luca Monticelli, Tel.: 403-220-4039; E-mail: luca.monticelli{at}ucalgary.ca.

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-oxo-nonanoic acid, and 12-oxo-9-dodecenoic 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 toward the water phase and the oxygen atoms form hydrogen bonds with water and the polar lipid headgroup. 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 toward 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.