Authors

Kazushige Yokoyama , Akane Ichiki

DOI: 10.54646/bijbnt.001

Abstract

The conformation of three amyloidogenic peptides; amyloid beta 1–40 (Aβ1−40), alpha synuclein (α-syn), and beta-2-microglobulin (β2m) are closely associated with the process of causing neurodegenerative diseases. Use of a peptide adsorbed gold nano-particle system allowed us to investigate the interactive segment of each peptide responsible for peptide-peptide networking, which is crucial to initiate the formation of an oligomer and leads to fibrillogenesis. The adsorption orientationof theamyloidogenic peptides onthe nano-goldcolloid spherical surface wasexplainedbysimulatinghowmuchareaofthemetalsurfacewascoveredbythepeptides,i.e.,coverageratio,Θ. The empirically extracted Θ was explained by the summation of the 1st layer and the 2nd layer with a spikingout orientation of the prolate. Of note, the involvement of the 2nd layer was peptide type dependent. The nanosize dependence of Θ was linearly correlated with available spacing between adjacent peptides, Sd, which were approximated as prolates, For Aβ1−40 and α-syn, the 2nd layer was more included as Sd increased. In contrast, β2m was found to gyrate over the gold surface as Sd increased, creating a partially positive (δ+) region and repelling the extra β2m from the surface. Thus, as Sd decreased, it prohibited the gyration of β2m resulting in less δ+ region, and more β2m monomers were adsorbed with δ+ segment as the 2nd layer than the case where β2m gyrates more under relatively larger Sd. Based on the trend found in an experimentally extracted Θ as a function of Sd, optimized charge distribution of Aβ1−40 and α-syn were concluded to be negative partial charge (δ−) region that was covered by the positive partial charge (δ+) region. However, β2m may have a relatively large and/or distributed δ+ region with a small portion of δ− at the one end of a prolate. The characterization made in this work confirmed current understandings on the formation of the protein corona over nano-particles. 

Keywords

Amyloidogenic peptides, gold nano-particles, protein folding, protein oligomerization, protein aggregation, protein corona.