Citrate-stabilized gold nanoparticles hinder fibrillogenesis of a pathological variant of β2-microglobulin

Cristina Cantarutti, Sara Raimondi, Giorgia Brancolini, Alessandra Corazza, Sofia Giorgetti, Maurizio Ballico, Stefano Zanini, Giovanni Palmisano, Paolo Bertoncin, Loredana Marchese, P. Patrizia Mangione, Vittorio Bellotti, Stefano Corni, Federico Fogolari, Gennaro Esposito

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Abstract

Nanoparticles have repeatedly been shown to enhance fibril formation when assayed with amyloidogenic proteins. Recently, however, evidence casting some doubt about the generality of this conclusion started to emerge. Therefore, to investigate further the influence of nanoparticles on the fibrillation process, we used a naturally occurring variant of the paradigmatic amyloidogenic protein β2-microglobulin (β2m), namely D76N β2m where asparagine replaces aspartate at position 76. This variant is responsible for aggressive systemic amyloidosis. After characterizing the interaction of the variant with citrate-stabilized gold nanoparticles (Cit-AuNPs) by NMR and modeling, we analyzed the fibril formation by three different methods: thioflavin T fluorescence, native agarose gel electrophoresis and transmission electron microscopy. The NMR evidence indicated a fast-exchange interaction involving preferentially specific regions of the protein that proved, by subsequent modeling, to be consistent with a dimeric adduct interacting with Cit-AuNPs. The fibril detection assays showed that AuNPs are able to hamper D76N β2m fibrillogenesis through an effective interaction that competes with protofibril formation or recruitment. These findings open promising perspectives for the optimization of the nanoparticle surface to design tunable interactions with proteins.

Original languageEnglish (US)
Pages (from-to)3941-3951
Number of pages11
JournalNanoscale
Volume9
Issue number11
DOIs
StatePublished - Mar 21 2017

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ASJC Scopus subject areas

  • Materials Science(all)

Cite this

Cantarutti, C., Raimondi, S., Brancolini, G., Corazza, A., Giorgetti, S., Ballico, M., Zanini, S., Palmisano, G., Bertoncin, P., Marchese, L., Patrizia Mangione, P., Bellotti, V., Corni, S., Fogolari, F., & Esposito, G. (2017). Citrate-stabilized gold nanoparticles hinder fibrillogenesis of a pathological variant of β2-microglobulin. Nanoscale, 9(11), 3941-3951. https://doi.org/10.1039/c6nr09362k