Impact of an Integral Membrane Protein on Asymmetric Lipid Membranes

Biological membranes are inherently asymmetric in lipid composition, a feature essential for membrane protein function. Recent studies revealed that the activity of the outer membrane enzyme phospholipase A (OmpLA) is modulated by lateral stress differences between membrane leaflets. However, the mechanistic link between membrane asymmetry and protein function remains incomplete, as proteininduced changes to bilayer structure, such as hydrophobic mismatch, are not fully understood. Here, we aim to investigate how OmpLA influences the structure of asymmetric lipid membranes using SANS with contrast variation and complementary SAXS. We will study
asymmetric and symmetric lipid vesicles with and without OmpLA, focusing on protein-induced membrane deformation, lipid scrambling, and protein self-association. By combining scattering data with MD simulations and NMR, this work will provide unprecedented insights into protein–lipid interactions in asymmetric membranes.