Product Spotlight: Role of Oxidized Lipids in Permeation of H2O2 Through a Lipid Membrane: Molecular Mechanism of an Inhibitor to Promoter Switch

Posted on July 07, 2021


Oxidized Lipids

Cell membranes are vital for protecting the cell's components from the extracellular environment and also for controlling what goes in and out of the cell. The cell membrane allows certain substances to enter and leave the cell via active or passive permeation. Active permeation requires energy to shuttle molecules against their concentration gradients; whiles, passive permeation requires no energy and takes advantage of multistep equilibria from outside the cell, through the outer leaflet, inner leaflet, and finally inside the cell. This passive permeation is sensitive to a molecule's chemical and physical properties and how they interact with the properties of the lipid bilayer.

Hydrogen peroxide (H2O2) is an important small molecule that has significant effects living organisms. H2O2 is regulated via diffusion across the cell membrane. The inside of the cell membrane is full of hydrophobic alkyl chains which causes the hydrophilic H2O2 molecule to minimally partition into the inner part of the cell membrane. The introduction of hydrophilic alkyl chains in this region greatly increases the ability of H2O2 to permeate the cell membrane. So, how can you incorporate hydrophilic alkyl chains into the inner cell membrane? You can use Avanti’s oxidized lipids as these researchers did! Incorporating oxidized lipids into the cell membrane alters the intra- and intermolecular configuration but the effect these changes have on H2O2 permeation is unclear. The following research aimed to elucidate this relationship.

The oxidized lipids that were incorporated into the cell membrane were POVPC, 16:0-09:0 (ALDO) PC, and PAzePC. Each of these lipids has two alkyl chains but is made more hydrophilic by an aldehyde or carboxylic acid moiety attached to the end of the shorter alkyl chain. These lipids were mixed with DOPC (10:1 DOPC:OxLipid) and the permeation of H2O2 was measured by a spectrofluorometer using chemiluminescence emitted from luminol and HRP that were also present inside the prepared liposomes.

The results of this study were interesting and two independent mechanisms of H2O2 permeation were elucidated. Liposomes doped with POVPC showed an intra-molecular switching from permeation enhancing to permeation inhibiting dependent on the mol percentage of POVPC present in the liposome. In contrast to POVPC, the presence of 16:0-09:0 (ALDO) PC, which contains longer alkyl chains but maintains the aldehyde group at its end, in DOPC liposomes only served as a permeation inhibitor regardless of concentration. Finally, the effect of the addition of PAzePC to DOPC liposomes was investigated. PAzePC has an alkyl chain length similar to 16:0-09:0 (ALDO) PC, but it contains a carboxylic acid rather than an aldehyde group. Thus, the effects of various functional groups was investigated. The presence of PAzePC was found to be permeating enhancing at any concentration. These studies provide the basis for further exploration of rationally designed artificial liposomes that can undergo a stimuli-responsive switching between permeation promoting and inhibiting which might make it possible to control release of small molecules.

Read the rest of this fascinating article HERE! And don’t forget to check out Avanti's Oxidized Lipids for all of your research needs!