PT  - JOURNAL ARTICLE
AU  - Arter, William E.
AU  - Xu, Catherine K.
AU  - Castellana-Cruz, Marta
AU  - Herling, Therese W.
AU  - Krainer, Georg
AU  - Saar, Kadi L.
AU  - Kumita, Janet R.
AU  - Dobson, Christopher M.
AU  - Knowles, Tuomas P. J.
TI  - Rapid Fractionation and Characterisation of Alpha-Synuclein Oligomers in Solution
AID  - 10.1101/2020.03.10.985804
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.03.10.985804
4099  - http://biorxiv.org/content/early/2020/03/14/2020.03.10.985804.short
4100  - http://biorxiv.org/content/early/2020/03/14/2020.03.10.985804.full
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.