Anti-fibrillation and trans-fibrillation activities of L-arginine modified magnetic nanoparticles on lysozyme.

Abstract

Over the last two decades, the application of nanoparticles (NPs) in the investigation of protein and peptide aggregation and amyloid-related diseases has been extensively studied. Here, we investigate anti-fibrillation and trans-fibrillation activities of L-Arginine modified Magnetic NPs (RMNPs, Fe₃O₄@Arg) on hen egg white lysozyme (HEWL) as a model protein and HEWL amyloid aggregate (HAA, i.e., aggregated HEWL fibrils). RMNPs were prepared by the co-precipitation method and subsequently characterized using X-ray diffraction (XRD), vibrating sample magnetometry (VSM), Fourier transform infrared spectroscopy (FT-IR), and scanning electron microscopy (SEM). The comparison was made among Arg, Magnetic NPs (MNPs), and RMNPs to explore their anti-fibrillation activities on HEWL. Using intrinsic tryptophan (Trp) and extrinsic thioflavin T (ThT) fluorescence assays, circular dichroism (CD) spectroscopy, and electron microscopy methods, for instance, we present the anti-fibrillation and trans-fibrillation activities of the RMNPs on HEWLs or HAAs. Accordingly, fibrillation was inhibited more than 80 percent, and fibrils were longitudinally rearranged to form late amyloid aggregates with a 57< nm diameter from early aggregates with a <14 nm diameter, respectively. The ability to inhibit HEWL amyloid formation highlights the concentration-dependent effects of the investigated NPs on HEWL at different stoichiometric ratios of MNPs and RMNPs. Moreover, RMNPs can interact with HEWL amyloids in vitro and alter the structure of the aggregates. Collectively, our findings shed light on the anti-fibrillation and trans-fibrillation effects of RMNPs on HEWL and HEWL amyloid aggregate (HAA), respectively. In this study, we aim to investigate the potential preventive effects of RMNPs on protein structural trans-formation and fibrillation, as well as their potential to promote the trans-fibrillation of resulting fibrils, representing a novel strategy to interfere with protein aggregation-related disorders.