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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.