RT Journal Article
SR Electronic
T1 Rapid Fractionation and Characterisation of Alpha-Synuclein Oligomers in Solution
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.03.10.985804
DO 10.1101/2020.03.10.985804
A1 Arter, William E.
A1 Xu, Catherine K.
A1 Castellana-Cruz, Marta
A1 Herling, Therese W.
A1 Krainer, Georg
A1 Saar, Kadi L.
A1 Kumita, Janet R.
A1 Dobson, Christopher M.
A1 Knowles, Tuomas P. J.
YR 2020
UL http://biorxiv.org/content/early/2020/03/14/2020.03.10.985804.abstract
AB Oligomeric intermediates are implicated as neurotoxins in the pathogenesis of protein mis-folding diseases. Structural, biophysical and biochemical characterisation of these species is challenging due to their heterogeneous and transient nature, and their typically low abun-dance. Here, we show that microfluidic free-flow electrophoresis is capable of separating heterogeneous oligomer mixtures on a timescale of seconds, at least two orders of magnitude faster than conventional techniques. This enables analysis of oligomer structural heterogeneity, zeta-potential and immunochemistry with minimal sample perturbation under physiologically-relevant conditions.