Lipid Oxidation: Role of Membrane Phase-Separated Domains

Area of Science:

• Biophysics
• Molecular Biology
• Computational Chemistry

Background:

• Lipid oxidation is linked to inflammatory and neurodegenerative diseases.
• Membrane phase separation into liquid-ordered (Lo) and liquid-disordered (Ld) domains impacts membrane function.
• Domain interfaces are implicated in pore formation, but mechanisms are unclear.

Purpose of the Study:

• To investigate the effect of lipid oxidation on membrane permeability.
• To evaluate permeability at Lo/Ld domain interfaces in heterogeneous membranes.
• To compare permeability changes in homogeneous versus heterogeneous membranes upon oxidation.

Main Methods:

• Atomistic molecular dynamics simulations were employed.
• Studied nonoxidized and oxidized homogeneous membranes (single-phase).
• Examined permeability at Lo/Ld interfaces with oxidized or nonoxidized Ld domains.

Main Results:

• A small addition (1.5%) of lipid aldehydes at Lo/Ld interfaces increased membrane permeability.
• Oxidized lipid aldehydes had no significant effect on homogeneous membranes.
• Heterogeneous membranes showed increased permeability specifically at domain interfaces.

Conclusions:

• Membrane domain interfaces are critical sites for oxidation-induced permeability changes.
• Oxidative stress effects on membranes are domain-dependent.
• Findings inform therapeutic strategies involving oxidative stress, such as plasma medicine and photodynamic therapy.