title: Imaging secondary structure of individual amyloid fibrils of a β2-microglobulin fragment using near-field infrared spectroscopy.
abstract: Amyloid fibril diseases are characterized by the abnormal production of aggregated proteins and are associated with many types of neuro- and physically degenerative diseases. X-ray diffraction techniques, solid-state magic-angle spinning NMR spectroscopy, circular dichroism (CD) spectroscopy, and transmission electron microscopy studies have been utilized to detect and examine the chemical, electronic, material, and structural properties of amyloid fibrils at up to angstrom spatial resolution. However, X-ray diffraction studies require crystals of the fibril to be analyzed, while other techniques can only probe the bulk solution or solid samples. In the work reported here, apertureless near-field scanning infrared microscopy (ANSIM) was used to probe the secondary structure of individual amyloid fibrils made from an in vitro solution. Simultaneous topographic and infrared images of individual amyloid fibrils synthesized from the #21-31 peptide fragment of β(2)-microglobulin were acquired. Using this technique, IR spectra of the amyloid fibrils were obtained with a spatial resolution of less than 30 nm. It is observed that the experimental scattered field spectrum correlates strongly with that calculated using the far-field absorption spectrum. The near-field images of the amyloid fibrils exhibit much lower scattering of the IR radiation at approximately 1630 cm(-1). In addition, the near-field images also indicate that composition and/or structural variations among individual amyloid fibrils were present.
authors.affiliation: Department of Chemistry, University of Toronto, Toronto, Ontario, Canada M5S 3H6.
authors.forename: Melissa
authors.initials: M
authors.lastname: Paulite
authors.forename: Zahra
authors.initials: Z
authors.lastname: Fakhraai
authors.forename: Isaac T S
authors.initials: IT
authors.lastname: Li
authors.forename: Nikhil
authors.initials: N
authors.lastname: Gunari
authors.forename: Adrienne E
authors.initials: AE
authors.lastname: Tanur
authors.forename: Gilbert C
authors.initials: GC
authors.lastname: Walker
mesh_terms: D000682:Amyloid / Q000737:chemistry / Q000648:ultrastructure*; D008744:Methylamines / Q000737:chemistry; D046529:Microscopy, Electron, Transmission; D015394:Molecular Structure; D017433:Protein Structure, Secondary; D017550:Spectroscopy, Fourier Transform Infrared; D001613:beta 2-Microglobulin / Q000737:chemistry / Q000648:ultrastructure*
chemical_list: D000682:Amyloid; D008744:Methylamines; D001613:beta 2-Microglobulin; C005855:trimethyloxamine