Citrate stabilized gold nanoparticles interfere with amyloid fibril formation: D76N and Δn6 β2-microglobulin variants

Giorgia Brancolini, Maria Celeste Maschio, Cristina Cantarutti, Alessandra Corazza, Federico Fogolari, Vittorio Bellotti, Stefano Corni, Gennaro Esposito

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4793-4806
Number of pages14
JournalNanoscale
Volume10
Issue number10
DOIs
StatePublished - Mar 14 2018

ASJC Scopus subject areas

  • Materials Science(all)

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    Brancolini, G., Maschio, M. C., Cantarutti, C., Corazza, A., Fogolari, F., Bellotti, V., Corni, S., & Esposito, G. (2018). Citrate stabilized gold nanoparticles interfere with amyloid fibril formation: D76N and Δn6 β2-microglobulin variants. Nanoscale, 10(10), 4793-4806. https://doi.org/10.1039/c7nr06808e