Detection of Protein Misfolding Using Nanorod Assemblies

PI：Nicholas A.Kotov Proposal Number：1403777机构：密歇根大学Ann Arbor标题：使用纳米棒组件检测蛋白质错误折叠神经退行性疾病，如阿尔茨海默氏症或克雅氏病(CJD)对患者、他们的亲属和卫生系统造成破坏性影响，给我们的社会带来了巨大的挑战。问题之一是，这些疾病不会引起任何免疫反应，因此，不能使用基于抗体检测的传统诊断方法。需要具有高度敏感性和选择性的新诊断方法。未来，在这项提议中开发的新工具可能会使阿尔茨海默氏症等神经退行性疾病的诊断成为可能。这些疾病的共同原因是纳米级生物分子--淀粉样多肽和蛋白质--自我组装成以低聚物和微米级纤维为代表的更大结构。我们将利用病原体的这种特性开发一种新的诊断技术，这种特性将在它们与无机纳米颗粒的相互作用中揭示出来。该项目将包括评估淀粉样多肽和蛋白质的两种自组装结构方法。第一种方法将利用均匀的金纳米棒自组装成大的超晶体，以及我们用它们制造大图案的能力。表面增强拉曼散射(SERS)将是我们区分良性和错误折叠多肽的关键光谱技术。第二种诊断方法将利用纳米棒对的手性，这种对可以旋转光的偏振。淀粉样多肽和其他物种会改变纳米棒之间的扭曲角度，这可以通过圆二色谱来检测。此外，还将对其与淀粉样肽纳米棒组装的光子特性进行完整的理论分析和表征。预期的影响将从理解纳米棒和多肽的自组织到更大的中尺度结构。我们还希望测试概念验证技术，以检测唾液和尿液中错误折叠的病原体。

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.