Interaction of ZnO Nanostructures with Proteins: In Vitro Fibrillation/Antifibrillation Studies and in Silico Molecular Docking Simulations

Abstract

Protein amyloidosis is related to many neurological disorders. Nanoparticles (NPs) due to their small size have the potential to modulate the protein monomers/oligomers assembly into fibril forms, as well as the disaggregation of preformed fibrils. Herein, we have synthesized ZnO nanoflowers and polyol-coated ZnO NPs of relatively small size (40 nm) with cylindrical shape, through solvothermal and microwave-assisted routes. The effect of the different morphology of nanostructures on the fibrillation/antifibrillation process was monitored in bovine serum albumin (BSA) and human insulin (HI) by fluorescence Thioflavin T (ThT) measurements. Although both nanomaterials affected the amyloid formation mechanism as well as their disaggregation, ZnO nanoflowers with their sharp edges exhibited the greatest amyloid degradation rate in both model proteins (73% and 35%, respectively) and inhibited the most the insulin fibril growth, while restrained also the fibrillation process in the case of albumin solution. In order to explain the described in vitro activity of ZnO nanostructures, we adopted in silico molecular docking studies on the crystal structure of BSA and HI. The binding energy of ZnO NPs was found lower for BSA (-5.44), highlighting their ability to act as catalysts in the fibrillation process of albumin monomers.

Strong Structural and Electronic Binding of Bovine Serum Albumin to ZnO via Specific Amino Acid Residues and Zinc Atoms

“…Here we conduct a comprehensive, systematic study on the adsorption process of BSA on various ZnO surfaces by atomic force microscopy (AFM) with molecular resolution as well as by force field (FF) and density‐functional tight‐binding (DFTB) calculations. Although, there is some research available on BSA adsorption on ZnO nanoparticles using other simulation methods such as molecular docking, [41,42] to the best of our knowledge, this is the first combined study on adsorption of BSA on various ZnO surfaces. ZnO atomic surface structure and chemistry are observed to have a pronounced effect on interactions at BSA‐ZnO interfaces.…”

Food Additive Zinc Oxide Nanoparticles: Dissolution, Interaction, Fate, Cytotoxicity, and Oral Toxicity

“…On the other hand, Singh et al demonstrated that the morphology (tetrapodal or spherical shape) of ZnO can be a critical factor preserving the functionality of proteins in the ZnO–protein corona [ 48 ]. Giannousi et al also showed that ZnO nanoflowers with sharp edges exhibited a higher amyloid degradation rate in the BSA and human insulin model proteins than ZnO NPs [ 49 ], which requires further extended investigation on a wide range of bio-matrices and NP types.…”

Alizarin and Purpurin from Rubia tinctorum L. Suppress Insulin Fibrillation and Reduce the Amyloid-Induced Cytotoxicity

“…In recent years, protein amyloid fibrillation has been a research hotspot in the field of biomedicine and pharmaceutical industry, which is related to many amyloidosis diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease, type 2 diabetes (T2D), etc. − For example, amyloid-β (Aβ) plaques are accumulated in the hippocampus and cerebral cortex of AD patients; α-synuclein (αSN) is the main component of Lewy bodies, whose accumulation plays a key role in the direct pathogenesis of PD; insulin amyloid deposits are often found in the frequent injection sites of T2D patients . Although different diseases have different amyloid proteins/peptides, studies have pointed out that the fibrotic aggregation process of amyloid follows a common nucleation growth mechanism, and the process can be divided into three stages: nucleation phase (the formation of oligomers), elongation phase (rapid growth of aggregates), and stationary phase (stable formation of fibrils) .…”