Membrane fission caused by lipid photooxidation

Cell membranes are dynamic structures essential for endocytosis and exocytosis, which involve membrane fission and fusion. While in biological systems these events are typically catalyzed by proteins such as clathrin and SNAREs, it is conceivable that specific elastic conditions of the membrane must be met to make them possible. Understanding the contribution of mechanical properties is therefore crucial to elucidating the physicochemical basis of membrane remodeling. 

This project investigates lipid photo-oxidation–induced fission in giant unilamellar vesicles (GUVs), with a focus on how oxidation reshapes membrane mechanics. To achieve this, we will employ micropipette aspiration, which allows direct measurement of thermodynamic parameters such as critical fission tension and membrane elasticity. This approach will enable us to determine whether oxidation-driven changes in bilayer mechanics are sufficient to trigger spontaneous fission in the absence of proteins.

Our model system will consist of GUVs containing mono- and polyunsaturated lipids (PUFAs), saturated lipids (DPPC), and cholesterol, subjected to oxidative stress by irradiation in the presence of photosensitizers of distinct polarity (methylene blue, hydrophilic; pheophorbide, hydrophobic). Preliminary results from our group show that PUFA oxidation promotes fission, suggesting that modifications in spontaneous curvature and elastic properties of the bilayer can substitute, under certain conditions, for the catalytic role of proteins.

We aim to map the critical conditions for fission across different lipid compositions,  evaluate cholesterol’s role in stabilizing or weakening lipid domains (Lo/Ld) under oxidative stress and compare the efficiency of hydrophilic versus hydrophobic photosensitizers in inducing fission.

By establishing a direct correlation between membrane mechanics and lipid oxidation, this work seeks to advance our fundamental understanding of lipid-mediated fission and fusion. Beyond basic biophysics, the findings may also shed light on pathological processes associated with oxidative stress, such as neurodegeneration, and support the design of light-based therapeutic strategies, including photodynamic therapy.