Surface-Tethered Curved Membrane Mimics for Characterizing Alpha Synuclein-Membrane Interactions by Surface Plasmon Resonance

Alpha-synuclein is a presynaptic neuronal protein that is genetically and neuropathologically linked to Parkinson’s disease (PD), playing a critical role in the development of neurodegenerative disorders through its tendency to self-aggregate. However, its membrane-binding dynamics, especially in response to membrane curvature, remain poorly understood. Herein, we report the development and application of a tunable, curved membrane system built on an optical sensor platform for surface plasmon resonance (SPR) characterization of the protein-membrane interactions of alpha synuclein. Vesicles of varied size, lipid compositions, and charges were immobilized at the interface, enabling precise control of the interface with properties relevant to the effects on binding characteristics. Incorporation of cholesterol, sphingomyelin, and ganglioside (GM1) allowed the investigation of protein binding in a more biologically relevant membrane environment. Finally, the impact of a disaggregation agent on alpha synuclein binding was characterized to understand the disruption process. Our results demonstrate the capability of the optical biosensing system for studying complex protein-membrane interactions and facilitating the understanding of curvature-sensitive binding by alpha-synuclein.