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

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Cofibrillization of Pathogenic and Functional Amyloid Proteins with Gold Nanoparticles against Amyloidogenesis
Biomacromolecules ( IF 5.5 ) Pub Date : 2017-11-14 00:00:00 , DOI: 10.1021/acs.biomac.7b01359
Ibrahim Javed ₁ , Yunxiang Sun ₂ , Jozef Adamcik ₃ , Bo Wang ₂ , Aleksandr Kakinen ₁ , Emily H. Pilkington ₁ , Feng Ding ₂ , Raffaele Mezzenga ₃ , Thomas P. Davis _{1,

4} , Pu Chun Ke ₁

Affiliation

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.

中文翻译：

与金纳米颗粒对淀粉样蛋白生成的致病性和功能性淀粉样蛋白的共纤化

仿生纳米复合材料和支架是广泛的生物医学应用的关键。在这里，我们首次展示了一种通过金纳米颗粒（AuNPs）将原发性和功能性淀粉样蛋白原纤维共纤化的简便方案及其对淀粉样蛋白生成的应用。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揭示了人类胰岛淀粉样多肽（IAPP）与AuNPs的β-乳球蛋白“电晕”之间的β-折叠堆叠，从而实现了该方案。仿生AuNPs消除了IAPP毒性，实现了IAPP淀粉样蛋白的X射线破坏，并允许对病原性淀粉样蛋白进行暗场成像以及人类T细胞对其免疫原性的反应。除了提供针对淀粉样蛋白生成的可行的新纳米技术外，不同病理的淀粉样蛋白之间的体内串扰。

更新日期：2017-11-15

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