Simultaneous fractionation and characterization of pre-fibrillar aggregates in solution with single-molecule microfluidics

Misfolding and aggregation of proteins is a phenomenon central to the pathology of a wide range of currently incurable disorders, in particular Alzheimer’s (AD) and Parkinson’s disease (PD). Oligomeric species forming during the aggregation reactions of amyloid-β peptide in AD and α-synuclein in PD have been identified as major cytotoxins linked to the pathogenesis of these diseases. However, due to their low abundance in aggregation mixtures and high instability and heterogeneity in terms of the number of constituent monomers, they are exceptionally difficult to characterise using most conventional biophysical techniques.