Single-vesicle imaging reveals lipid-selective and stepwise membrane disruption by monomeric α-synuclein
Artikel i vetenskaplig tidskrift, 2020

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 concentrations down to 10 nM (∼100 proteins per vesicle). In contrast, phosphatidylserine vesicles were only marginally affected. These insights into structural consequences of α-synuclein interaction with lipid vesicles highlight the contrasting roles of different anionic lipids, which may be of mechanistic relevance for both normal protein function (e.g., synaptic vesicle binding) and dysfunction (e.g., mitochondrial membrane interaction).

single-vesicle scattering

lipid vesicle

membrane interaction

α-synuclein

Författare

Jonas Hannestad

Chalmers, Fysik, Biologisk fysik

Sandra Rocha

Chalmers, Biologi och bioteknik, Kemisk biologi

Björn Agnarsson

Chalmers, Fysik, Nano- och biofysik

Vladimir Zhdanov

Chalmers, Fysik, Nano- och biofysik

Russian Academy of Sciences

Pernilla Wittung Stafshede

Chalmers, Biologi och bioteknik, Kemisk biologi

Fredrik Höök

Chalmers, Fysik, Nano- och biofysik

Proceedings of the National Academy of Sciences of the United States of America

0027-8424 (ISSN) 1091-6490 (eISSN)

Vol. 117 25 14178-14186

Ämneskategorier

Fysikalisk kemi

Biokemi och molekylärbiologi

Biofysik

DOI

10.1073/pnas.1914670117

PubMed

32513706

Mer information

Senast uppdaterat

2020-09-18