Biophysical Society Thematic Meeting - October 25-30, 2015

Polymers and Self Assembly: From Biology to Nanomaterials Poster Session II

45-POS Board 45 Combining Single-Molecule Techniques with Microfluidics to Study Protein Aggregation Linked to Neurodegenerative Disease Christopher Taylor , Mathew Horrocks, Tuomas Knowles, David Klenerman. University of Cambridge, Cambridge, United Kingdom. Alzheimer’s and Parkinson’s diseases, along with numerous other neurodegenerative diseases, are understood to be caused by the aggregation of amyloidogenic proteins in the brain. This protein self-assembly produces cytotoxic species that give rise to brain deterioration. Recent evidence indicates that it is the rare, low-molecular-weight species (oligomers) rather than the more abundant high-molecular-weight fibrils of certain amyloidogenic proteins that are the most cytotoxic in a number of neurodegenerative diseases. Due to their low relative abundance, transient nature and high heterogeneity, oligomers have proven a challenging target for biophysical studies. We have approached this problem by uniting the advantages of single- molecule fluorescence, which can resolve sub-populations of species by probing each individually, and microfluidics. By using a microfluidic device to rapidly dilute protein samples for single-molecule detection, we are able to observe unstable species which would otherwise be invisible. The combination of the two methods enables the determination of the size distribution of the oligomers, their stability and information on their structure as the aggregation proceeds. This fundamental information on the aggregation pathway and the rate constants measured will shed insight into the pathogenesis of Alzheimer's or Parkinson's disease.

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