Membrane-Protein-Hydration Interaction of α-Synuclein with Anionic Vesicles Probed via Angle-Resolved Second Harmonic Scattering.

Amyloid formation of the protein alpha-synuclein promotes neurodegeneration in Parkinson's disease. The normal function of alpha-synuclein includes synaptic vesicle transport and fusion, and the protein binds strongly to negatively charged vesicles in vitro. Here, we demonstrate that nonresonant angle-resolved second-harmonic scattering detects alpha-synuclein binding to liposomes through changes in water orientational correlations and can thus be used as a high-accuracy and high-throughput label-free probe of protein-liposome interactions. The obtained results support a binding model in which the N-terminus of alpha-synuclein adopts an alpha-helical conformation that lies flat on the vesicle surface while the negatively charged C-terminus remains in solution.