title: Molecular simulations of the effects of phospholipid and cholesterol peroxidation on lipid membrane properties.
abstract: Non-enzymatic lipid peroxidation may change biomembrane structure and function. Here, we employed molecular dynamics simulations to study the effects of either phospholipid or cholesterol peroxidation individually, as well as the combined peroxidation of both components. When lipids were peroxidized, the generated OOH groups migrated to the membrane surface and engaged in H-bonds with each other and the phospholipid carbonyl ester groups. It caused the sn-2 acyl chains of phospholipid hydroperoxides to bend and the whole sterol backbone of cholesterol hydroperoxides to tilt. When phospholipids were kept intact, peroxidation of the sterol backbone led to a partial degradation of its condensing and ordering properties, independently of the position and isomerism of the OOH substitution. However, even in massively peroxidized membranes in which all phospholipids and cholesterol were peroxidized, the condensing and ordering properties of the sterol backbone were still significant. The possible implications for the formation of membrane lateral domains were discussed. Cholesterol peroxyl radicals were also investigated and we found that the OO groups did not migrate to the headgroups region.
authors.affiliation: Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Avenida dos Estados 5001, CEP 09210-580 Santo André, SP, Brazil.
authors.forename: Antenor J P
authors.initials: AJP
authors.lastname: Neto
authors.affiliation: Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Avenida dos Estados 5001, CEP 09210-580 Santo André, SP, Brazil. Electronic address: rodrigo.cordeiro@ufabc.edu.br.
authors.forename: Rodrigo M
authors.initials: RM
authors.lastname: Cordeiro
mesh_terms: D002784:Cholesterol / Q000737:chemistry*; D015227:Lipid Peroxidation; D008567:Membranes, Artificial; D056004:Molecular Dynamics Simulation; D010743:Phospholipids / Q000737:chemistry*
chemical_list: D008567:Membranes, Artificial; D010743:Phospholipids; D002784:Cholesterol
keywords: Cholesterol; Hydroperoxide; Lipid bilayer; Molecular dynamics simulation; Oxidative stress; Oxysterol