Vesicle explosion under light-induced asymmetric oxidation*

Oxidation of lipids by reactive oxygen species (ROS) alters their structural properties, compromising lipid-bilayer integrity, disrupting homeostasis in living cells, and even causing the cell death. Oxidation of a model membranes employing giant unilamellar vesicles (GUVs), leads to the formation of a series of short-lived pores as well as total catastrophic loss of membrane stability. However, the understanding of how the lipid oxidation leads to GUVs destabilization is lacking. In this talk, we will discuss the response of GUVs to the oxidation of lipids caused by photo-generated ROS in presence of a photosensitizer. We show that only under the asymmetric oxidation conditions, the GUVs develop micron-sized short-lived pores or exhibit vesicle explosion (i.e., the sudden catastrophic collapse of vesicles). Utilizing numerical modeling of pore-opening dynamics we link the oxidation-induced conformational changes in lipid to the generated spontaneous curvature, and demonstrate its critical role GUVs explosion. We further discuss the non-monotonic temporal evolution of spontaneous curvature. Finally, we will present a phase diagram delineating vesicle explosion and short-lived pore formation. Insights from our experiments and theoretical model have the potential to enhance the fundamental understanding of the stability of biological membranes in oxidative environments as well as aid in precision  drug delivery.