Unraveling the Speciation of β-Amyloid Peptides during the Aggregation Process by Taylor Dispersion Analysis

Aggregation mechanisms of amyloid beta peptides depend on multiple intrinsic and extrinsic physicochemical factors (e.g., peptide chain length, truncation, peptide concentration, pH, ionic strength, temperature, metal concentration, etc.). Due to this high number of parameters, the formation of oligomers and their propensity to aggregate make the elucidation of this physiopathological mechanism a challenging task. From the analytical point of view, up to our knowledge, few techniques are able to quantify, in real time, the proportion and the size of the different soluble species during the aggregation process. This work aims at demonstrating the efficacy of the modern Taylor dispersion analysis (TDA) performed in capillaries (50 mu m i.d.) to unravel the speciation of beta-amyloid peptides in low-volume peptide samples (similar to 100 mu L) with an analysis time of similar to 3 min per run. TDA was applied to study the aggregation process of A beta(1-40) and A beta(1-42) peptides at physiological pH and temperature, where more than 140 data points were generated with a total volume of similar to 1 mu L over the whole aggregation study (about 0.5 mu g of peptides). TDA was able to give a complete and quantitative picture of the A beta speciation during the aggregation process, including the sizing of the oligomers and protofibrils, the consumption of the monomer, and the quantification of different early- and late-formed aggregated species.

Automated summary

This study demonstrates the efficacy of modern Taylor dispersion analysis (TDA) in unraveling the speciation of beta-amyloid peptides in low-volume peptide samples with a short analysis time. TDA was able to provide a complete and quantitative picture of A beta speciation during the aggregation process, including the sizing of oligomers and protofibrils, the consumption of monomers, and the quantification of different early and late-formed aggregated species.