Single-vesicle imaging reveals lipid-selective and stepwise membrane disruption by monomeric α-synuclein.

ABSTRACT: The interaction of the neuronal protein α-synuclein with lipid membranes appears crucial in the context of Parkinson's disease, but the underlying mechanistic details, including the roles of different lipids in pathogenic protein aggregation and membrane disruption, remain elusive. Here, we used single-vesicle resolution fluorescence and label-free scattering microscopy to investigate the interaction kinetics of monomeric α-synuclein with surface-tethered vesicles composed of different negatively charged lipids. Supported by a theoretical model to account for structural changes in scattering properties of surface-tethered lipid vesicles, the data demonstrate stepwise vesicle disruption and asymmetric membrane deformation upon α-synuclein binding to phosphatidylglycerol vesicles at protein

SUBMITTER: Hannestad JK 

PROVIDER: S-EPMC7322013 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature