Nanopore Analysis of β-Amyloid Peptide Aggregation Transition Induced by Small Molecules

beta-Amyloid 42 (A beta 42) is the predominant form of the amyloid peptide, which is found in the plaques of the brains of Alzheimer's (AD) patients and is one of the most abundant components in amyloid aggregates. Information of the A beta 42 aggregation states is essential for developing an understanding of the pathologic process of amyloidoses. Here, we used alpha-hemolysin (alpha-HL) pores to probe the different aggregation transition of A beta 42 in the presence of beta-cyclodextrin (beta-CD), a promoter of A beta 42 aggregations, and in the presence of Congo red (CR), an inhibitor of aggregations. Analyzing the characteristic transit duration times and blockade currents showed that beta-CD and CR have opposite effects on the aggregation of A beta 42. Translocation events of the monomeric A beta 42 peptide were significantly lower in amplitude currents than protofilaments, and protofilaments were captured in the alpha-HL nanopore with a longer duration time. CR binds to A beta 42 and its peptide fibrils by reducing the aggregated fibrils formation. In this process it is assumed CR interferes with intermolecular hydrogen bonding present in the aggregates. In contrast to CR, beta-CD promotes the aggregation of A beta 42. These differences can readily be analyzed by monitoring the corresponding characteristic blockade events using a biological alpha-HL nanopore.