The density of anionic lipids modulates the adsorption of α-Synuclein onto lipid membranes

alpha-Synuclein is an intrinsically disordered presynaptic protein associated with Parkinson's disease. The physiological role of alpha-Synuclein is not fully understood, but the protein is known to interact with lipid membranes. We here study how membrane charge affects the adsorption of alpha-Synuclein to (i) supported lipid bilayers and (ii) small unilamellar vesicles with varying amounts of anionic lipids. The results showed that alpha-Synuclein adsorbs onto membranes containing >= 5% anionic phosphatidylserine (DOPS) lipids, but not to membranes containing <= 1% DOPS. The density of adsorbed alpha-Synuclein increased steadily with the DOPS content up to 20% DOPS, after which it leveled off. The vesicles were saturated with alpha-Synuclein at a 3-5 times higher protein density compared to the supported bilayers, which suggests that a more deformable membrane binds more alpha-Synuclein. Altogether, the results show that both membrane charge density and flexibility influence the association of alpha-Synuclein to lipid membranes.