title: Nanoscale Heterogeneity of the Molecular Structure of Individual hIAPP Amyloid Fibrils Revealed with Tip-Enhanced Raman Spectroscopy.
abstract: Type 2 diabetes mellitus is characterized by the pathological deposition of fibrillized protein, known as amyloids. It is thought that oligomers and/or amyloid 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 distinguish 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 spectroscopy (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 structure reveals a highly heterogeneous surface structure. Finally, TERS can probe fibrils formed on a lipid interface, which is more representative of amyloids in vivo.
authors.affiliation: FOM Institute AMOLF, Science Park 104, 1098, XG, Amsterdam, The Netherlands.
authors.forename: Corianne C
authors.initials: CC
authors.lastname: vandenAkker
authors.affiliation: Leibniz Institute of Photonic Technology, Albert-Einstein-Straße 9, 07745, Jena, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Deckert-Gaudig
authors.affiliation: Department of Molecular Spectroscopy, Max Planck Institute for Polymer Research, Ackermannweg 10, 55128, Mainz, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Schleeger
authors.affiliation: Soft Condensed Matter, Debye Institute for Nanomaterials Science, Department of Physics and Astronomy, Utrecht University, Princetonplein 5, 3584, CC, Utrecht, The Netherlands.|Unilever Research Labs, NL-3133 AT Vlaardingen, The Netherlands.
authors.forename: Krassimir P
authors.initials: KP
authors.lastname: Velikov
authors.affiliation: Leibniz Institute of Photonic Technology, Albert-Einstein-Straße 9, 07745, Jena, Germany.|Institute for Physical Chemistry and Abbe Center of Photonics, University of Jena, Helmholtzweg 4, 07743, Jena, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Deckert
authors.affiliation: Department of Molecular Spectroscopy, Max Planck Institute for Polymer Research, Ackermannweg 10, 55128, Mainz, Germany.
authors.forename: Mischa
authors.initials: M
authors.lastname: Bonn
authors.affiliation: FOM Institute AMOLF, Science Park 104, 1098, XG, Amsterdam, The Netherlands.
authors.forename: Gijsje H
authors.initials: GH
authors.lastname: Koenderink
mesh_terms: D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry*; D006801:Humans; D058228:Islet Amyloid Polypeptide / Q000737:chemistry* / Q000378:metabolism; D008055:Lipids / Q000737:chemistry; D018625:Microscopy, Atomic Force; D017348:Microscopy, Electron, Scanning Transmission; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017550:Spectroscopy, Fourier Transform Infrared; D013059:Spectrum Analysis, Raman / Q000379:methods*; D013499:Surface Properties
chemical_list: D000682:Amyloid; D058228:Islet Amyloid Polypeptide; D008055:Lipids
keywords: TERS; amylin; amyloid fibrils, protein misfolding; islet amyloid polypeptides; protein nanofibrils