Detection of Protein Misfolding Using Nanorod Assemblies

PI：Nicholas A. Kotov提案编号：1403777机构：密歇根大学安娜堡分校题目：使用纳米棒组装检测蛋白质错误折叠神经退行性疾病，如阿尔茨海默氏症帕金森氏症或克雅氏病（CJD）对我们的社会构成了巨大的挑战，因为它们对患者，他们的亲属和卫生系统造成了毁灭性的影响。 其中一个问题是这些疾病不诱导任何免疫反应，因此，不能使用基于抗体检测的传统诊断方法。需要高度敏感和选择性的新诊断方法。 在未来，在该提案期间开发的新工具可能能够诊断神经退行性疾病，如阿尔茨海默氏症。 这些疾病的共同原因是纳米级生物分子-淀粉样肽和蛋白质-自组装成以寡聚体和微米级纤维为代表的较大结构。我们将开发一种新的诊断技术，利用病原体的这种特性，这些特性将在它们与无机纳米颗粒的相互作用中揭示出来。 该项目将涉及评估淀粉样肽和蛋白质自组装结构的两种方法。 第一个将利用均匀的金纳米棒自组装成大的超晶体，以及我们用它们制作大图案的能力。 表面增强拉曼散射（Sers）将是关键的光谱技术，使我们能够区分良性和错误折叠的肽。 第二种诊断方法将利用纳米棒对的手性，可以旋转光的偏振。 淀粉样肽和其他物质会改变纳米棒之间的扭转角，这可以通过圆二色光谱检测到。此外，完整的理论分析和表征其光子特性的纳米棒组件与淀粉样肽将进行。 预期的影响将从理解纳米棒和肽的自组织到更大的介观结构。 我们还希望测试概念验证技术，以检测唾液和尿液中的错误折叠病原体。

PI: Nicholas A. KotovProposal Number: 1403777Institution: University of Michigan Ann ArborTitle: Detection of Protein Misfolding Using Nanorod AssembliesNeurodegenerative diseases, such as Alzheimer's Parkinson's or Creutzfeldt-Jakob diseases (CJD) pose a great challenge for our society because of their devastating impact on patients, their relatives, and health system. One of the problems is that these diseases do not induce any immunological response and thus, traditional diagnostics methods based on antibody detection cannot be used. New methods of diagnostics that are highly sensitive and selective are required. In the future, novel tools developed during this proposal may enable diagnosis of neurodegenerative diseases such as Alzheimer's. The common cause of these diseases is self-assembly of the nanoscale biological molecules - amyloid peptides and proteins - into larger structures represented by oligomers and micrometer scale fibers. We shall develop a new diagnostics technique utilizing this property of the disease agents that will be revealed in their interactions with inorganic nanoscale particles. The project will involve evaluation of two methods of self-assembled structures of amyloid peptides and proteins. The first one will take advantage of self-assembly of uniform gold nanorods into large supercrystals and our ability to make large patterns with them. Surface enhanced Raman scattering (SERS) will be the key spectroscopic technique that would allow us to differentiate benign and misfolded peptides. The second diagnostics method will take advantage of chirality of nanorod pairs that can rotate the polarization of light. Amyloid peptides and other species will change the twisting angle between the nanorods that can be detected by the circular dichroism spectroscopy. Additionally, complete theoretical analysis and characterization of their photonic properties of nanorod assemblies with amyloid peptides will be carried out. The expected impact will range from the understanding of self-organization of nanorods and peptides into larger mesoscale structures. We also expect to test the proof-of-concept techniques to detect the misfolded disease agents in saliva and urine.