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金纳米粒子共纤化致病性和功能性淀粉样蛋白以对抗淀粉样变性。

Cofibrillization of Pathogenic and Functional Amyloid Proteins with Gold Nanoparticles against Amyloidogenesis.

机构信息

ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University , 381 Royal Parade, Parkville, Victoria 3052, Australia.

Department of Physics and Astronomy, Clemson University , Clemson, South Carolina 29634, United States.

出版信息

Biomacromolecules. 2017 Dec 11;18(12):4316-4322. doi: 10.1021/acs.biomac.7b01359. Epub 2017 Nov 14.

Abstract

Biomimetic nanocomposites and scaffolds hold the key to a wide range of biomedical applications. Here we show, for the first time, a facile scheme of cofibrillizing pathogenic and functional amyloid fibrils via gold nanoparticles (AuNPs) and their applications against amyloidogenesis. This scheme was realized by β-sheet stacking between human islet amyloid polypeptide (IAPP) and the β-lactoglobulin "corona" of the AuNPs, as revealed by transmission electron microscopy, 3D atomic force microscopy, circular dichroism spectroscopy, and molecular dynamics simulations. The biomimetic AuNPs eliminated IAPP toxicity, enabled X-ray destruction of IAPP amyloids, and allowed dark-field imaging of pathogenic amyloids and their immunogenic response by human T cells. In addition to providing a viable new nanotechnology against amyloidogenesis, this study has implications for understanding the in vivo cross-talk between amyloid proteins of different pathologies.

摘要

仿生纳米复合材料和支架为广泛的生物医学应用提供了关键。在这里,我们首次展示了一种通过金纳米粒子(AuNPs)共纤化致病和功能淀粉样纤维的简便方案,以及其在抗淀粉样变性方面的应用。该方案通过人胰岛淀粉样多肽(IAPP)与 AuNPs 的β-乳球蛋白“冠”之间的β-折叠堆积来实现,这一点通过透射电子显微镜、3D 原子力显微镜、圆二色性光谱和分子动力学模拟得到了揭示。仿生 AuNPs 消除了 IAPP 的毒性,使 X 射线能够破坏 IAPP 淀粉样纤维,并通过人 T 细胞进行致病淀粉样纤维及其免疫原性反应的暗场成像。除了提供一种可行的新纳米技术来对抗淀粉样变性外,这项研究还对理解不同病理学中淀粉样蛋白的体内相互作用具有重要意义。

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