title: Alpha-tocopherol inhibits pore formation in oxidized bilayers.
abstract: In biological membranes, alpha-tocopherols (α-toc; vitamin E) protect polyunsaturated lipids from free radicals. Although the interactions of α-toc with non-oxidized lipid bilayers have been studied, their effects on oxidized bilayers remain unknown. In this study, atomistic molecular dynamics (MD) simulations of oxidized lipid bilayers were performed with varying concentrations of α-toc. Bilayers with 1-palmitoyl-2-lauroyl-sn-glycero-3-phosphocholine (PLPC) lipids and their aldehyde derivatives at a 1 : 1 ratio were studied. Our simulations show that oxidized lipids self-assemble into aggregates with a water pore rapidly developing across the bilayer. The free energy of transporting an α-toc molecule in a bilayer suggests that α-tocs can passively adsorb into it. When α-toc molecules were present at low concentrations in bilayers containing oxidized lipids, water pore formation was slowed down. At high α-toc concentrations, no pores were observed. Based on the simulations, we propose that the mechanism of how α-toc inhibits pore formation in bilayers with oxidized lipids is the following: α-tocs trap the polar groups of the oxidized lipids at the membrane-water interface resulting in a decreased probability of the oxidized lipids making contact with the two leaflets and initiating pore formation. This demonstrates that α-toc molecules not only protect the bilayer from oxidation but also help to stabilize the bilayer after lipid peroxidation occurs. These results will help in designing more efficient molecules to protect membranes from oxidative stress.
authors.affiliation: Department of Physics, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand. jirasak.w@ku.ac.th and Computational Biomodelling Laboratory for Agricultural Science and Technology (CBLAST), Faculty of Science, Kasetsart University, Bangkok 10900, Thailand.
authors.forename: Phansiri
authors.initials: P
authors.lastname: Boonnoy
authors.affiliation: Department of Mathematics and Computer Science & Institute for Complex Molecular Systems, Eindhoven University of Technology, MetaForum, 5600 MB Eindhoven, The Netherlands and Departments of Chemistry and Applied Mathematics, Western University, 1151 Richmond Street, London, Ontario N6A 5B7, Canada.
authors.forename: Mikko
authors.initials: M
authors.lastname: Karttunen
authors.affiliation: Department of Physics, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand. jirasak.w@ku.ac.th and Computational Biomodelling Laboratory for Agricultural Science and Technology (CBLAST), Faculty of Science, Kasetsart University, Bangkok 10900, Thailand and Thailand Center of Excellence in Physics (ThEP Center), Commission on Higher Education, Bangkok 10400, Thailand.
authors.forename: Jirasak
authors.identifier: http://orcid.org/0000-0002-3651-9870
authors.initials: J
authors.lastname: Wong-Ekkabut
mesh_terms: D002462:Cell Membrane / Q000378:metabolism; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism*; D015227:Lipid Peroxidation; D056004:Molecular Dynamics Simulation; D010084:Oxidation-Reduction; D014867:Water / Q000737:chemistry; D024502:alpha-Tocopherol / Q000737:chemistry* / Q000378:metabolism
chemical_list: D008051:Lipid Bilayers; D014867:Water; D024502:alpha-Tocopherol