Single Molecule Tools for Probing Protein Aggregation

Protein aggregation poses a fundamental problem in biophysics, whose solutions have enormous potential for societal benefits. Many devastating and incurable diseases, such as Alzheimer''s, Parkinson''s and Type II diabetes, are strongly linked to the misfolding and aggregation of specific proteins. The links between misfolding, aggregation and toxicity, with clues spread across fields from physics and physical chemistry to clinical science and epidemiology, have remained difficult to decipher. In addition, the transience of the aggregation intermediates makes it a difficult challenge. Optical spectroscopy and microscopy, providing unparalleled sensitivity and resolution, are two of the few tools which have been able to provide some effective leads in understanding the process. Here we present a short summary of the applications of fluorescence correlation spectroscopy and total internal reflection fluorescence microscopy to this problem, primarily focusing on the progress made in our laboratory.