Lipid Oxidation: Role of Membrane Phase-Separated Domains

J Chem Inf Model. 2021 Jun 28;61(6):2857-2868. doi: 10.1021/acs.jcim.1c00104. Epub 2021 Jun 3.

Abstract

Lipid oxidation is associated with several inflammatory and neurodegenerative diseases, but many questions to unravel its effects on biomembranes are still open due to the complexity of the topic. For instance, recent studies indicated that phase-separated domains can have a significant effect on membrane function. It is reported that domain interfaces are "hot spots" for pore formation, but the underlying mechanisms and the effect of oxidation-induced phase separation on membranes remain elusive. Thus, to evaluate the permeability of the membrane coexisting of liquid-ordered (Lo) and liquid-disordered (Ld) domains, we performed atomistic molecular dynamics simulations. Specifically, we studied the membrane permeability of nonoxidized or oxidized homogeneous membranes (single-phase) and at the Lo/Ld domain interfaces of heterogeneous membranes, where the Ld domain is composed of either oxidized or nonoxidized lipids. Our simulation results reveal that the addition of only 1.5% of lipid aldehyde molecules at the Lo/Ld domain interfaces of heterogeneous membranes increases the membrane permeability, whereas their addition at homogeneous membranes does not have any effect. This study is of interest for a better understanding of cancer treatment methods based on oxidative stress (causing among others lipid oxidation), such as plasma medicine and photodynamic therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Membrane
  • Humans
  • Lipid Bilayers*
  • Lipid Metabolism
  • Membrane Microdomains
  • Molecular Dynamics Simulation*
  • Oxidation-Reduction

Substances

  • Lipid Bilayers