"Effects of Oxidized Lipids on the Biophysical Properties of Bilayer Membrane Models"
Oxidized phospholipids (oxPC) that arise from oxidative stress contribute to many diseases including cardiovascular, neurodegenerative, and metabolic disorders. Specific oxPC species, KDdiA-PC and KOdiA-PC, have been implicated in the buildup of fatty deposits in arterial walls (atherosclerosis) that can lead to more serious cardiovascular conditions like heart attack and stroke. Both oxPC are found in small low-density lipoprotein particles where they exist in monolayers alongside non-oxidized unsaturated phospholipids and free cholesterol. However, they can also exist in much larger and more complex lipid bilayers like those that comprise cell membranes. These oxPC are well-characterized in low-density lipoproteins, but how they affect the biophysical properties of cell membranes remains unclear. To discern these effects in membrane models, we use a variety of biophysical techniques (fluorescence microscopy, quartz crystal microbalance with dissipation monitoring) and all-atom molecular dynamics. Here we show that vesicles containing either KDdiA-PC or KOdiA-PC form planar bilayers in a different manner than vesicles containing non-oxidized species, and that increasing the concentration of either oxidized species in both experimental and simulated membrane models results in conformational changes that affect overall membrane structure and stability. Ascertaining the effects oxPC in lipid bilayer models contributes to a comprehensive view of what is occurring in cell membranes at the molecular level. This information is crucial to understanding the role of lipid oxidation in cardiovascular disease as well as other diseases associated with oxidative stress.