Picking Up Good Vibes: Following Structural Dynamics of Fibril Aggregation with Two-Dimensional Infrared Spectroscopy

Amyloid fibril aggregation is linked to diseases such as type II diabetes, Alzheimer\u27s, Parkinson\u27s, and rheumatoid arthritis. In particular, human islet amyloid polypeptide (hIAPP) fibril aggregation in pancreatic β cells is correlated with type II diabetes, but its aggregation mechanism is not well understood. Because vibrations are sensitive to secondary structure, two-dimensional infrared spectroscopy (2D IR) along with residue-specific isotope labeling can be used to track structural changes in hIAPP as it forms the final fibril structure. We will discuss Prof. Martin Zanni\u27s work using these techniques to elucidate both the general mechanism of fibril formation and the way in which potential inhibitors interact with hIAPP. Knowledge of these processes will allow for rational drug design of inhibitors to combat fibril aggregation