The Chaperone Potential of Protein Nanoparticles

Abstract

Protein chaperones play a very important role in the body. When other proteins become unfolded, misfolded or denatured (non-native) they expose hydrophobic domains that are normally hidden from the aqueous solvent. Exposure of these domains can lead to irreversible protein aggregation, which is the basis of protein aggregation diseases such as Huntington’s disease. Protein chaperones can prevent protein aggregation and their key role in disease is a basis of biomedical research.
Attention has focused on nanotechnology in recent years because of the unique properties afforded by their small scale, such as a vastly improved surface to volume ratio. This has led to applications in medicine such as drug delivery vehicles. Recently the application of metal-based and hyrdogel nanoparticles as surrogate protein chaperones has also been investigated.
Within this project, existing protein nanoparticles have been made and tested for chaperone ability with remarkable results; they are currently the only synthetic protein nanoparticles to have been shown to have this function. They have chaperoned successfully against protein aggregation of two heat denatured client proteins: citrate synthase at 44° and γ-crystallin at 70°. They have also prevented filament-filament interactions, representing a unique function of the biological sHSPs that is manifested in these nanoparticles.
In these experiments they have therefore shown themselves to be highly effective over a range of different protein concentrations and temperatures and with a range of different client proteins and macromolecular assemblies. The nanoparticle outperformed a natural protein chaperone in both the heat denaturation and filament-filament association assays. These nanoparticles have exciting potential in the biopharmaceutical and protein stabilisation industries.