Lipid Oxidation: Role of Membrane Phase-Separated Domains

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.