Nanoscale Heterogeneity of the Molecular Structure of Individual hIAPP Amyloid Fibrils Revealed with Tip-Enhanced Raman Spectroscopy

in: Small (2015)
Deckert-Gaudig, Tanja; Schleeger, Michael; Velikov, Krassimir P.; Deckert, Volker; Bonn, Mischa; Koenderink, Gijsje H.; van den Akker, Corianne C.
Type 2 diabetes mellitus is characterized by the pathological deposition of fibrillized protein, known as amyloids. It is thought that oligomers and/or amy- loid fibrils formed from human islet amyloid polypeptide (hIAPP or amylin) cause cell death by membrane damage. The molecular structure of hIAPP amyloid fibrils is dominated by β-sheet structure, as probed with conventional infrared and Raman vibrational spectroscopy. However, with these techniques it is not possible to dis- tinguish between the core and the surface structure of the fibrils. Since the fibril surface crucially affects amyloid toxicity, it is essential to know its structure. Here the surface molecular structure and amino acid residue composition of hIAPP fibrils are specifically probed with nanoscale resolution using tip-enhanced Raman spec- troscopy (TERS). The fibril 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 struc- ture reveals a highly heterogeneous surface structure. Finally, TERS can probe fib- rils formed on a lipid interface, which is more representative of amyloids in vivo.

Third party cookies & scripts

This site uses cookies. For optimal performance, smooth social media and promotional use, it is recommended that you agree to third party cookies and scripts. This may involve sharing information about your use of the third-party social media, advertising and analytics website.
For more information, see privacy policy and imprint.
Which cookies & scripts and the associated processing of your personal data do you agree with?

You can change your preferences anytime by visiting privacy policy.