Membrane curvature enhances oxidation within lipid bilayers in a composition-dependent manner

Oxidative stress drives lipid peroxidation in cellular membranes, but the combined influence of membrane curvature and composition remains poorly defined. Using reconstituted lipid vesicles and a fluorescent oxidation probe, we show that lipid peroxidation is enhanced in smaller vesicles (i.e., highly curved membranes). The oxidation rate increases with unsaturated lipids, while cholesterol suppresses this effect. Measurements of membrane packing and diffusivity support these findings, demonstrating how curvature and composition together govern membrane susceptibility to oxidative damage. These results provide new insight into the physicochemical basis of membrane stability under oxidative stress and have broad implications for understanding the vulnerability of curved cellular membranes.