Inhibition of Human Serum Albumin Fibrillation by Two-Dimensional Nanoparticles

Abstract

The formation and deposition of amyloid fibrils have been linked to the pathogenesis of numerous debilitating neurodegenerative disorders. Serum albumins serve as good model proteins for understanding the molecular mechanisms of protein aggregation and fibril formation. Graphene-based nanotherapeutics appear to be promising candidates for designing inhibitors of protein fibrillation. The inhibitory effect of graphene oxide (GO) nanoparticles on the fibrillation of human serum albumin (HSA) in an in vitro mixed solvent system has been investigated. The methods used include ThT fluorescence, ANS binding, Trp fluorescence, circular dichroism, fluorescence microscopy, field-emission scanning electron microscopy, and high-resolution transmission electron microscopy. It was observed that GO inhibits HSA fibrillation and forms agglomerates with β-sheet rich prefibrillar species. Binding of GO prevents the formation of mature fibrils with characteristic cross-β sheet but does not promote refolding to the native state.