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Rapid Structural, Kinetic, and Immunochemical Analysis of Alpha-Synuclein Oligomers in Solution.

Accepted version
Peer-reviewed

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Authors

Castellana-Cruz, Marta 
Herling, Therese W 
Krainer, Georg 

Abstract

Oligomers comprised of misfolded proteins are implicated as neurotoxins in the pathogenesis of protein misfolding conditions such as Parkinson's and Alzheimer's diseases. Structural, biophysical, and biochemical characterization of these nanoscale protein assemblies is key to understanding their pathology and the design of therapeutic interventions, yet it is challenging due to their heterogeneous, transient nature and low relative abundance in complex mixtures. Here, we demonstrate separation of heterogeneous populations of oligomeric α-synuclein, a protein central to the pathology of Parkinson's disease, in solution using microfluidic free-flow electrophoresis. We characterize nanoscale structural heterogeneity of transient oligomers on a time scale of seconds, at least 2 orders of magnitude faster than conventional techniques. Furthermore, we utilize our platform to analyze oligomer ζ-potential and probe the immunochemistry of wild-type α-synuclein oligomers. Our findings contribute to an improved characterization of α-synuclein oligomers and demonstrate the application of microchip electrophoresis for the free-solution analysis of biological nanoparticle analytes.

Description

Keywords

Alpha-synuclein, aptamer, free-flow electrophoresis, microfluidics, oligomer, Alzheimer Disease, Humans, Parkinson Disease, alpha-Synuclein

Journal Title

Nano Lett

Conference Name

Journal ISSN

1530-6984
1530-6992

Volume Title

20

Publisher

American Chemical Society (ACS)

Rights

All rights reserved
Sponsorship
European Research Council (337969)
Engineering and Physical Sciences Research Council (EP/L015978/1)
European Commission Horizon 2020 (H2020) Marie Sk?odowska-Curie actions (841466)