Phospholipid Monolayers and Vesicular Membranes Show Only Minor Structural Changes After Interaction With α...

We study how the lipid membrane structure changes upon interaction with $\alpha$ -synuclein (aSyn) at low and physiological concentrations, using three different X-ray scattering methods and two well-established model systems, the Langmuir film balance and small unilamellar vesicles in bulk solution. While aSyn is highly membrane active, we find that at physiological protein concentration it induces only rather small changes in lipid membrane structure and vesicle shape. The vertical density profile of Langmuir lipid monolayers shows no observable changes for DPPC:DPPS and DOPC:DOPS, and moderate changes only for a model system containing gangliosides. Contrarily, the protein induces more pronounced changes in the bilayer density profile of highly curved anionic lipid vesicles, but without rupture and major remodeling of vesicular shapes as reported previously for pathological concentrations. In fact, the shape of the vesicles showed even a slight reduction in ellipticity. In addition to aSyn only, we also study the structure of the monolayer and vesicular membranes in the presence of two major synaptic proteins, aSyn and synapsin 1, at concentrations where the latter induces lipid-protein condensates.