Effect of Silica Nanoparticles on the Amyloid Fibrillation of Lysozyme

Abstract

Protein fibrils are regarded as undesired products as these are associated with numerous neuro- and non-neurodegenerative disorders. Increasing evidence suggests that the mechanism of fibrillation involves the formation of various oligomeric intermediates, which are known to be more toxic than mature fibrils. Here, we report the impact of synthesized silica nanoparticles (SiNPs) of diameters ∼52 nm on the aggregation behavior of hen egg white lysozyme (HEWL) under heat and acidic conditions. Congo red as well as ThT binding assays and AFM imaging studies indicate that SiNPs trigger the amyloid formation of HEWL in a dose-dependent manner. ThT kinetic studies and FTIR studies suggest that the fibrillation kinetics does not involve the formation of toxic oligomeric intermediates at higher concentrations of SiNPs. By measuring fluorescence lifetime values of the bound ThT, SiNP-induced fibrillation of HEWL can easily be realized. CD spectroscopic studies indicate that native HEWL becomes unfolded upon incubation under the experimental conditions and is rapidly converted into the β-sheet-rich fibrillar aggregates in the presence of SiNPs with increasing concentrations. It has been further revealed that fibrillar aggregates formed at higher concentrations of SiNPs preferably adopt an antiparallel β-sheet configuration. The enhanced fibrillation in the presence of SiNPs is likely because of preferential adsorption of the non-amyloidogenic regions of HEWL, resulting in the exposure of the aggregation-prone regions of HEWL toward the solvent. The study will provide deeper insights into the evolution of oligomer-free fibrillation that can be useful to demonstrate the underlying mechanism of amyloid fibrillation.

<p>Protein–Nanoparticle Interaction: Corona Formation and Conformational Changes in Proteins on Nanoparticles</p>

“…73 Hen egg white lysozyme was unfolded by silica NPs, resulting in the formation of β-sheet-rich fiber-like protein aggregates. 74 Thus, the knowledge of the functionality of NPs demands an understanding of the conformational changes in the protein corona of each NP system (Figure 2).…”

Adsorption and Conformation Behavior of Lysozyme on a Gold Surface Determined by QCM-D, MP-SPR, and FTIR

“…For instance, adsorption of blood proteins on some materials not adapted to biomedical applications can lead to thrombosis [ 1 , 2 ], in the chromatography technique, it provides the opportunity for phases separation [ 3 , 4 ], while in the biotechnological area, it can act as the basis for designing biosensors [ 5 , 6 , 7 , 8 ]. It was also noticed that interactions between proteins and surfaces could induce the formation or stabilization of structures characteristic for neurodegenerative diseases [ 9 , 10 , 11 ]. Therefore, control of the stability of protein structures has great potential for their use in neurological diagnostics.…”

Inhibition of Glycation-Induced Aggregation of Human Serum Albumin by Organic–Inorganic Hybrid Nanocomposites of Iron Oxide-Functionalized Nanocellulose

“…10,11 Destabilization of the native structure of proteins is responsible for many diseases and can be favored by a change in pH, high temperature, electrostatic interactions, presence of salts, surfactants, and metal ions, change in osmolyte concentration, high pressure, ionic strength, and so on, which may result in the formation of misfolded intermediates, which are otherwise inaccessible under normal physiological conditions. 12−15 The formation of partially unfolded or destabilized structures ultimately results in the formation of aggregated proteins. As the protein aggregation is associated with several human diseases, it has attracted the interest of material scientists and biotechnologists to look for fibrillation inhibitory measures from a biomedical perspective.…”