Inhibition of lysozyme fibrillation by human serum albumin nanoparticles: Possible mechanism

Abstract

Amyloid fibrillation is a prevalent phenomenon in different proteins and peptides, which results in a variety of disorders. Over the last decade, implementation of nanoparticles (NPs), with or without drugs, is considered as a promising approach to protect against the aggregation process of amyloid proteins. In this study, we investigated the effect of human serum albumin NPs (HSA NPs) on the fibrillation of Hen Egg White Lysozyme (HEWL). The results showed that HSA NPs decrease the fibrillation of HEWL in a size dependent manner. Surprisingly, despite their inhibitory effects on the formation of long fibrils, our studies revealed that the NPs do not preserve the stability of the protein’s structure in denaturing conditions. In fact, different structural analysis methods revealed that in the presence of the NPs, the protein’s tendency to expose hydrophobic patches increased. Therefore, it seems that HSA NPs are responsible for decrease in HEWL fibrillation by reducing its concentration and blocking hot spot regions for self-assembly via moderate interaction. Collectively, our results shed light on the impact of HSA NPs on HEWL fibrillation and open new challenges on the implications of these NPs for drug delivery purposes or direct use as therapeutic agents.