Type 2 diabetes mellitus is characterized by the pathological deposition of fi brillized protein, known as amyloids. It is thought that oligomers and/or amyloid fi brils formed from human islet amyloid polypeptide (hIAPP or amylin) cause cell death by membrane damage. The molecular structure of hIAPP amyloid fi brils is dominated by β-sheet structure, as probed with conventional infrared and Raman vibrational spectroscopy. However, with these techniques it is not possible to distinguish between the core and the surface structure of the fi brils. Since the fi bril surface crucially affects amyloid toxicity, it is essential to know its structure. Here the surface molecular structure and amino acid residue composition of hIAPP fi brils are specifi cally probed with nanoscale resolution using tip-enhanced Raman spectroscopy (TERS). The fi bril surface mainly contains unordered or α-helical structures, in contrast to the β-sheet-rich core. This experimentally validates recent models of hIAPP amyloids based on NMR measurements. Spatial mapping of the surface structure reveals a highly heterogeneous surface structure. Finally, TERS can probe fi brils formed on a lipid interface, which is more representative of amyloids in vivo.

Weinheim: Wiley
V. Subramaniam (Vinod)
Biological Soft Matter-Former Group

vandenAkker, C. C., Deckert-Gaudig, T., Schleeger, M., Velikov, K., Deckert, V., Bonn, M., & Koenderink, G. (2015). Nanoscale Heterogeneity of the Molecular Structure of Individual hIAPP Amyloid Fibrils Revealed with Tip-Enhanced Raman Spectroscopy. Small, 11(33), 4131–4139. doi:10.1002/smll.201500562