The Effect of Nanoparticles on Amyloid Aggregation Depends on the Protein Stability and Intrinsic Aggregation Rate

Abstract

Nanoparticles interfere with protein amyloid formation. Catalysis of the process may occur due to increased local protein concentration and nucleation on the nanoparticle surface, whereas tight binding or a large particle/protein surface area may lead to inhibition of protein aggregation. Here we show a clear correlation between the intrinsic protein stability and the nanoparticle effect on the aggregation rate. The results were reached for a series of five mutants of single-chain monellin differing in intrinsic stability toward denaturation, for which a correlation between protein stability and aggregation propensity has been previously documented by Szczepankiewicz et al. [Mol. Biosyst.20107 (2), 521–532]. The aggregation process was monitored by thioflavin T fluorescence in the absence and presence of copolymeric nanoparticles with different hydrophobic characters. For mutants with a high intrinsic stability and low intrinsic aggregation rate, we find that amyloid fibril formation is accelerated by nanoparticles. For mutants with a low intrinsic stability and high intrinsic aggregation rate, we find the opposite—a retardation of amyloid fibril formation by nanoparticles. Moreover, both catalytic and inhibitory effects are most pronounced with the least hydrophobic nanoparticles, which have a larger surface accessibility of hydrogen-bonding groups in the polymer backbone.

Influence of Aromatic Residues on the Material Characteristics of Aβ Amyloid Protofibrils at the Atomic Scale

“…dimer and trimer), and Ab-derived diffusible ligands) have more toxic characteristics than the fibrillars tructures. [16][17][18] Preand proto-fibrillar structures of amyloids are composed of highly orderedc ross-beta strands, stacked along the perpendicular axis. [5] These amyloidp refibrillar structures exist in various sizes, ranging from nano-to microscale due to the repetitive accumulation of fractured protofibrils under temperature and thermal fluctuations.…”

Nanoparticles in relation to peptide and protein aggregation

“…20 Changes in protein conformation upon binding with nanoparticles, or increased local protein concentration on the nanoparticle surfaces could promote aggregation, while trapping of early aggregation intermediates may inhibit further aggregation. 21 Nanoparticles possess huge amounts of Gibb's free energy, which enhances their adsorption capacities. The conjugation of proteins to nanoparticles not only stabilizes the system, but also introduces biocompatible functionalities to these particles for further biological interactions or coupling.…”

Investigation of the effects of carbon-based nanomaterials on A53T alpha-synuclein aggregation using a whole-cell recombinant biosensor

“…While several studies show that NPs with different structures interact with proteins and affect their aggregation, [22][23][24][25][26] there are limited data on the interaction of αS with NPs. Some recent findings in this regard include the acceleration of αS fibrillation in the presence of αS-conjugated CdSe/ZnS quantum dots, 27 the interactions of αS with negatively and positively charged gold NPs, 28,29 the effect of negatively charged Au NPs with different sizes on the interaction of NPs, 30 the effect of bare and surface-coated magnetic iron oxide (Fe 3 O 4 ) NPs on αS aggregation 31 and the influence of chemical composition and the amount and nature of the particle's surface on the nucleation phase of αS aggregation.…”