BOHR International Journal of Biocomputing and Nano Technology 2020, Vol. 1, No. 1, pp. 21–28 Copyright © 2021 BOHR Publishers https://doi.org/10.54646/bijbnt.006 www.bohrpub.com A Model for Nano-Scale Spherical Surface Coverage and Protein Corona Formation By Amyloidogenic Peptides Kazushige Yokoyama 1,∗ and Akane Ichiki 1,2 1 Department of Chemistry, The State University of New York Geneseo College,Geneseo, NY, USA 2 Center for iPS Cell Research and Application, Kyoto University, Kyoto Japan ∗ Corresponding author: yokoyama@geneseo.edu Abstract. The conformation of three amyloidogenic peptides; amyloid beta 1–40 (Aβ 1−40 ), 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 orientation of the amyloidogenic peptides on the nano-gold colloid spherical surface was explained by simulating how much area of the metal surface was covered by the peptides, i.e., coverage ratio, Θ. The empirically extracted Θ was explained by the summation of the 1 st layer and the 2 nd layer with a spiking- out orientation of the prolate. Of note, the involvement of the 2 nd layer was peptide type dependent. The nano- size dependence of Θ was linearly correlated with available spacing between adjacent peptides, S d , which were approximated as prolates, For Aβ 1−40 and α-syn, the 2 nd layer was more included as S d increased. In contrast, β2m was found to gyrate over the gold surface as S d increased, creating a partially positive (δ+) region and repelling the extra β2m from the surface. Thus, as S d decreased, it prohibited the gyration of β2m resulting in less δ+ region, and more β2m monomers were adsorbed with δ+ segment as the 2 nd layer than the case where β2m gyrates more under relatively larger S d . Based on the trend found in an experimentally extracted Θ as a function of S d , optimized charge distribution of Aβ 1−40 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 aggre- gation, protein corona. 1 Introduction The amyloidogenic peptides are hallmarks of neurodegen- erative diseases. Networking of the peptides is considered to be a critical process of the formation of fibrillogenesis [1, 2]. Although many intense studies have been conducted on the fibrils or oligomer formations of the amyloido- genic peptides, exact and clear characterization of an initial step of peptide networking has not been concluded. Neu- rodegenerative diseases, such as Alzheimer’s disease or Parkinson’s disease, are generally understood to be caused by an association of amyloidogenic peptides, such as amy- loid beta 1–40 or amyloid beta 1–42 (Aβ 1−40 or Aβ 1−42 ), or α-synuclein (α-syn), respectively. The formation of fib- rils pathologic to brain cell was known to be caused by the polymerization of an oligomer constructing the parts of a fiber (fibril). Thus, all fibrillogenesis originates from the formation of oligomers [3, 4, 5, 6, 7]. However, the initial formation of an oligomer needs to have an interac- tion between peptides, which has not been investigated in detail due to the challenge that initial oligomer formation is regarded as transient and involving very unstable inter- mediates. Our group conducted a series of studies focusing on the peptide networking, which can be critical for an oligomer formation, by utilizing amyloidogenic peptides coated gold nano-colloid. The approach we took was to prepare 21