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Title: Citrate stabilized gold nanoparticles interfere with amyloid fibril formation: D76N and ΔN6 β2-microglobulin variants

Journal Article · · Nanoscale
DOI:https://doi.org/10.1039/c7nr06808e· OSTI ID:1493591
ORCiD logo [1]; ORCiD logo [1];  [2];  [3]; ORCiD logo [3];  [4];  [5]; ORCiD logo [6]
  1. CNR Institute Nanoscience, Modena (Italy)
  2. Univ. of Udine, Udine (Italy)
  3. Univ. of Udine, Udine (Italy); Istituto Nazionale Biostrutture e Biosistemi, Roma (Italy)
  4. Univ. di Pavia, Pavia (Italy); Istituto Nazionale Biostrutture e Biosistemi, Roma (Italy); Univ. College of London, London (United Kingdom)
  5. Univ. of Padova, Padova (Italy); CNR Institute Nanoscience, Modena (Italy)
  6. CNR Institute Nanoscience, Modena (Italy); Istituto Nazionale Biostrutture e Biosistemi, Roma (Italy); New York Univ. at Abu Dhabi, Abu Dhabi (United Arab Emirates)
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Here, protein aggregation including the formation of dimers and multimers in solution, underlies an array of human diseases such as systemic amyloidosis which is a fatal disease caused by misfolding of native globular proteins damaging the structure and function of affected organs. Different kind of interactors can interfere with the formation of protein dimers and multimers in solution. A very special class of interactors are nanoparticles thanks to the extremely efficient extension of their interaction surface. In particular citrate-coated gold nanoparticles (cit-AuNPs) were recently investigated with amyloidogenic protein β2-microglobulin (β2m). Here we present the computational studies on two challenging models known for their enhanced amyloidogenic propensity, namely ΔN6 and D76N β2m naturally occurring variants, and disclose the role of cit-AuNPs on their fibrillogenesis. The proposed interaction mechanism lies in the interference of the cit-AuNPs with the protein dimers at the early stages of aggregation, that induces dimer disassembling. As a consequence, natural fibril formation can be inhibited. Relying on the comparison between atomistic simulations at multiple levels (enhanced sampling molecular dynamics and Brownian dynamics) and protein structural characterisation by NMR, we demonstrate that the cit-AuNPs interactors are able to inhibit protein dimer assembling. As a consequence, the natural fibril formation is also inhibited, as found in experiment.

Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States). National Energy Research Scientific Computing Center (NERSC)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES)
Grant/Contract Number:
AC02-05CH11231
OSTI ID:
1493591
Journal Information:
Nanoscale, Vol. 10, Issue 10; ISSN 2040-3364
Publisher:
Royal Society of ChemistryCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 25 works
Citation information provided by
Web of Science

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Cited By (7)

Interaction of gold nanosurfaces/nanoparticles with collagen-like peptides journal January 2019
Impact of nanoparticles on amyloid peptide and protein aggregation: a review with a focus on gold nanoparticles journal January 2018
A protein corona primer for physical chemists journal October 2019
Building Minimalist Models for Functionalized Metal Nanoparticles journal July 2019
Loosening of Side-Chain Packing Associated with Perturbations in Peripheral Dynamics Induced by the D76N Mutation of β2-Microglobulin Revealed by Pressure-NMR and Molecular Dynamic Simulations journal September 2019
Multiscale Molecular Dynamics Simulation of Multiple Protein Adsorption on Gold Nanoparticles journal July 2019
Low-Resolution Models for the Interaction Dynamics of Coated Gold Nanoparticles with β2-microglobulin journal August 2019

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