Nanoparticles as catalysts for protein fibrillation

Abstract

The study by Linse et al. (1) published in this issue of PNAS observes that nanoparticles (NPs) can significantly enhance the rate of protein fibrillation, or the formation of fibrils, potentially leading to novel mechanisms for amyloid diseases as well as therapeutic opportunities for their treatment. NPs are materials with dimensions between 1 and 100 nm whose small sizes confer properties distinct from those of bulk systems (2–5). Their potential to induce protein fibrillation is a function of both the NP surface charge, which promotes adherence of the protein, and its large surface area. In this case, NP–protein binding induces significant structural and functional perturbations to the protein, a fact that could be important for a more general understanding of the biological interactions of engineered NPs. The observation of fibrillation, which is a specific kind of aggregation phenomenon relevant for amyloid proteins, raises the possibility that NPs could play a role in increased risk of amyloidosis and other protein-misfolding diseases (Fig. 1). The authors call for further research into the potential for NPs to accelerate protein fibrillation and acknowledge that the same variables associated with new protein assemblies of this sort may have beneficial or even therapeutic roles. Artistic rendering of amyloid protein fibrillation in the presence of nanoparticles. The formation and deposition in the body's tissues of highly ordered, thread-like amyloid protein aggregates have been linked to a family of diseases. For example, fibrillation of insulin has been linked to diabetes. Linse et al. (1) studied 70-nm polymer particles and β2m protein, which in its normal state is an ≈3-nm globular protein; however, the dimensions and morphology for insulin fibrils on mica were the basis for this imagery (28). (A) Depicted here are large NPs (blue) and an amyloid protein (green) in its monomeric and …