Interfacial charge transfer with exfoliated graphene inhibits fibril formation in lysozyme amyloid

Abstract

Amyloid fibrillation is known to contribute in a variety of diseases including neurodegenerative disorders (e.g., Alzheimer's and Parkinson's disease) and type II diabetes. The inhibition of fibrillation has been suggested as a possible therapeutic strategy to prevent neuronal and pancreatic β-cell death associated with amyloid diseases. To this end, strong hydrophobic and π-π interactions between proteins and nanomaterials at the nanobio interface could be used to mitigate the stacking of amyloid structures associated with fibrillation. In this study, the authors show that exfoliated graphene effectively inhibits the formation of amyloid fibrils using a model amyloid-forming protein, viz., hen egg white lysozyme (HEWL). While previous theoretical models posit that hydrophobic and π-π stacking interactions result in strong interactions between graphene and proteins, the authors experimentally identified the presence of additional interfacial charge transfer interactions between HEWL and graphene using micro-Raman spectroscopy and Kelvin probe force microscopy. Their photoluminescence spectroscopy and transmission electron microscopy studies evince that the interfacial charge transfer combined with hydrophobic and π-π stacking interactions, specifically between the nanomaterial and the amino acid tryptophan, increase HEWL adsorption on graphene and thereby inhibit amyloid fibrillation.

Adsorption Behaviors of Typical Proteins on BP, GR, and C2N Surfaces

“…This behavior did not affect the secondary structure of proteins. The interaction between proteins and GR surfaces has been frequently studied, and the results of these studies are similar to those of our study. ,− The interactions between a BBA protein and the BP and C 2 N were thus simulated to verify the universality of the biological interactions observed between the proteins and the BP and C 2 N surfaces, as shown in Figure S5. The results showed that the BBA protein can also migrate on the BP surface without severe damage to its structure, which is consistent with the results of a previous study on the interaction between proteins and BP .…”

Advances in graphene-based nanoplatforms and their application in Parkinson's disease

“…53 Graphene oxide quantum dots, similarly to carbon quantum dots (CQDs), 54 also inhibited fibrillation in a model amyloid-forming protein hen egg-white lysozyme in a dose-dependent manner, presumably through interfacial charge transfer. 55 Indeed, GBNs can sequester both α-syn monomers and mature fibrils on their surface and thus inhibit its fibrillation (both nucleation and elongation) and disaggregate the fibrils. This prevents α-syn misfolding, fibrillation and aggregation that holds promises against α-syn pathology-induced neurodegeneration (Fig.…”

Therapeutic Potential of Nanomedicine in Management of Alzheimer’s Disease and Glioma

“… 129 , 130 The charge on the graphene plays a vital role in inhibition of fibril formation, the charge may be transferred to the aromatic residue of protein amino acid. 131 Carbon dots (CDs) have demonstrated potential to cross the BBB, due to presence of amino and carboxylic acid group on their surface that can be conjugated with CNS drugs, 132 making them an ideal nanocarrier to deliver the drugs in CNS to treat glioma and AD. Yellow-emissive CDs and graphene quantum dots were able to prevent the aggregation of Aβ in neuronal cells linked to tramiprosate.…”