Processes that produce reactive oxygen species (ROS) are ubiquitous in biology. Unsaturated lipids in cell membranes represent a major target for reaction with ROS. Oxidation of these lipid species has consequences for the structure and properties of membranes, and has significant implications related to the dysfunction of cellular processes resulting from oxidative damage. In membranes containing polyunsaturated lipids, oxidative processes can lead to tail group cleavage. This produces two molecular products: a larger species with the headgroup and a single intact tail, and a smaller species derived from the cleaved tail. Our studies have shown that upon replacing less than 3% of the unsaturated lipids in a synthetic bilayer with the larger of these species, the permeability of the membrane to small molecules increases by an order of magnitude. However, if the smaller tailgroup-derived species are included, the membrane barrier properties are significantly recovered. Oxidation of unsaturated lipids can also lead to a series of changes in area per lipid in a bilayer. As area per lipid changes, membrane tension is altered. We have shown that the oxidative alteration of membrane tension can be treated as a two-step process. In the first step, oxidated lipid tails are modified with hydrophilic groups, leading to an increase in area per lipid and a decrease in membrane tension. As oxidation continues, the tail groups are cleaved completely, reducing area per lipid and increasing membrane tension. Simultaneous with this increase in surface tension is a decrease in lipid line tension. These two effects synergistically lead to the formation of micron-scale pores in synthetic bilayers. Finally, our recent work has shown that oxidation can radically alter the phase behavior of phosphatidylethanolamine (PE) lipids. In biological systems, these lipids facilitate the formation of high-curvature membrane structures necessary for cell function. This high curvature is reflected in the inverse hexagonal phase that the lipids take on in water. We have shown that upon oxidation, PE lipids undergo molecular changes that allow them to take on a lamellar phase in water. Interestingly, at moderate water concentrations, these oxidized PE lipids also form previously unobserved micron-scale cubic structures.

Consequences of lipid oxidation on bilayer structural and mechanical properties

251st National Meeting (2016)

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