Multiplexed Digital Characterization of Misfolded Protein Oligomers via Solid-State Nanopores
Sarah E. Sandler, Robert I. Horne, Sara Rocchetti, Robert W. Novak, Nai‐Shu Hsu, Marta Castellana Cruz, Z. Faidon Brotzakis, Rebecca C. Gregory, Sean Chia, Gonçalo J. L. Bernardes, Ulrich F. Keyser, Michele Vendruscolo
Abstract
Misfolded protein oligomers are of central importance in both the diagnosis and treatment of Alzheimer's and Parkinson's diseases. However, accurate high-throughput methods to detect and quantify oligomer populations are still needed. We present here a single-molecule approach for the detection and quantification of oligomeric species. The approach is based on the use of solid-state nanopores and multiplexed DNA barcoding to identify and characterize oligomers from multiple samples. We study α-synuclein oligomers in the presence of several small-molecule inhibitors of α-synuclein aggregation as an illustration of the potential applicability of this method to the development of diagnostic and therapeutic methods for Parkinson's disease.