Significance: The ability of proteins to self-assemble into different types of fibrils with distinct morphologies has been linked to the pathological and clinical heterogeneity of amyloid diseases such as Alzheimer’s disease and Parkinson’s disease. Here, we describe nanoparticles (NPs) that efficiently label amyloid fibrils produced in vitro or isolated from postmortem tissues, under hydrating conditions and in such a way as to unmask their polymorphism and morphological features. Using these NPs, we show that pathological aggregates exhibit exceptional morphological homogeneity compared with amyloid fibrils produced in vitro, consistent with the emerging view that the physiologic milieu is a key determinant of amyloid fibril strains. These advances pave the way for elucidating the structural basis of amyloid strains and toxicity.

Course-grained simulations studies showed environmental-dependency of the mechanism of ubiquitin corona formation on gold nanoparticles and ubiquitin binding modalities, and a nanoparticle size-dependency of ubiquitin conformational changes and aggregation propensity.

A multiscale molecular dynamics simulation study has been carried out in order to provide in-depth information on the adsorption of hemoglobin, myoglobin, and trypsin over citrate-capped AuNPs of 15 nm diameter. In particular, determinants for single proteins adsorption and simultaneous adsorption of the three types of proteins considered have been studied by Coarse-Grained and Meso-Scale molecular simulations, respectively. The results, discussed in the light of the controversial experimental data reported in the current experimental literature, have provided a detailed description of the (i) recognition process, (ii) number of proteins involved in the early stages of corona formation, (iii) protein competition for AuNP adsorption, (iv) interaction modalities between AuNP and protein binding sites, and (v) protein structural preservation and alteration.