Detection of Protein Misfolding Using Nanorod Assemblies

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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.