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.

Hesperidin attenuates altered redox homeostasis in an experimental hyperlipidaemic model of rat

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Photosensitized Membrane Permeabilization Requires Contact-Dependent Reactions between Photosensitizer and Lipids

“…In fact, when Anderson and Krinsky first reported in the 1970's that liposomes could be lysed by photooxidation, they already questioned whether or not 1 O 2 was the major player in this phenomenon 31 . Secondly, and contrary to the popular belief that 1 O 2 -derived lipid hydroperoxides permeabilize membranes, there is growing experimental and computational evidence showing that lipid hydroperoxides form stable membranes that sustain chemical gradients 22,[32][33][34][35] . Thirdly, phospholipid aldehydes bearing truncated fatty-acyl chains have been shown to disrupt chemical gradients when incorporated to membrane mimetic systems and in molecular dynamics simulations 32,34,[36][37][38] .…”

Insight from Molecular dynamic simulation of reactive oxygen species in oxidized skin membrane

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