Field-induced droplet ionization illuminates stepwise oxidation of cell membrane lipids by hydroxyl radicals at the air-water interface

Life depends on the cell membranes that provide not just a container, but serve many important functions, not least of which is providing support for protein machinery that regulates mol. transport across the boundary. Oxidative damage of membrane components can lead to cellular dysfunction and potentially trigger cell death. In the current study, mechanistic details of the oxidn. of key cellular membrane components by hydroxyl radicals (OH) in monolayer lipid assemblies at the air-water interface are investigated for the first time using field-induced droplet ionization mass spectrometry (FIDI-MS). Products from OH oxidn. of lipids possessing both unsatd. and satd. carbon atoms are identified, and distinct mechanisms are proposed for reactions at these sites. Addn. of antioxidants to the lipid layers permits an assessment of their ability to inhibit oxidn. Remarkably, cholesterol, which often comprises 20-30% of cell membranes, is found to be a highly effective antioxidant. Cardiolipin alone is shown to be highly resistant to oxidn. owing to the tightly packed structure it forms in membranes, making it less surprising that nature selected this unique lipid as a major component of the inner membrane of mitochondria. Mol. dynamics simulations help to rationalize many of these observations.