Laboratory of Nano-Biophysics, Clemson Nanomaterials Institute, Anderson, South Carolina 29625.
Biointerphases. 2020 Jun 3;15(3):031010. doi: 10.1116/6.0000019.
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.
淀粉样纤维沉淀被认为与多种疾病相关,包括神经退行性疾病(如阿尔茨海默病和帕金森病)和 2 型糖尿病。抑制纤维沉淀已被认为是一种可能的治疗策略,可预防与淀粉样蛋白疾病相关的神经元和胰岛β细胞死亡。为此,在纳米生物界面,蛋白质和纳米材料之间的强疏水性和π-π 相互作用,可以用于减轻与纤维沉淀相关的淀粉样结构的堆积。在这项研究中,作者表明,使用模型淀粉样蛋白形成蛋白,即鸡卵清溶菌酶(HEWL),剥离的石墨烯可有效抑制淀粉样纤维的形成。虽然之前的理论模型假设疏水性和π-π 堆积相互作用会导致石墨烯与蛋白质之间产生强烈的相互作用,但作者通过微拉曼光谱和 Kelvin 探针力显微镜实验鉴定了 HEWL 和石墨烯之间存在额外的界面电荷转移相互作用。他们的光致发光光谱和透射电子显微镜研究表明,界面电荷转移与疏水性和π-π 堆积相互作用(特别是纳米材料与色氨酸之间的相互作用)相结合,增加了 HEWL 在石墨烯上的吸附,从而抑制了淀粉样纤维沉淀。