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.
