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

Cantarutti, C; Raimondi, S; Brancolini, G; Corazza, A; Giorgetti, S; Ballico, M; Zanini, S; ... Esposito, G; + view all (2017) Citrate-stabilized gold nanoparticles hinder fibrillogenesis of a pathological variant of β2-microglobulin. Nanoscale , 9 (11) pp. 3941-3951. 10.1039/c6nr09362k. Green open access

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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.

Type: Article
Title: Citrate-stabilized gold nanoparticles hinder fibrillogenesis of a pathological variant of β2-microglobulin
Open access status: An open access version is available from UCL Discovery
DOI: 10.1039/c6nr09362k
Publisher version: http://doi.org/10.1039/c6nr09362k
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation
URI: https://discovery.ucl.ac.uk/id/eprint/1549797
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