Spectroscopic Signature for Stable β-Amyloid Fibrils versus β-Sheet-Rich Oligomers

Abstract

We use two-dimensional IR (2D IR) spectroscopy to explore fibril formation for the two predominant isoforms of the β-amyloid (Aβ1–40 and Aβ1–42) protein associated with Alzheimer’s disease. Two-dimensional IR spectra resolve a transition at 1610 cm−1 in Aβ fibrils that does not appear in other Aβ aggregates, even those with predominantly β-sheet-structure-like oligomers. This transition is not resolved in linear IR spectroscopy because it lies under the broad band centered at 1625 cm−1, which is the traditional infrared signature for amyloid fibrils. The feature is prominent in 2D IR spectra because 2D lineshapes are narrower and scale nonlinearly with transition dipole strengths. Transmission electron microscopy measurements demonstrate that the 1610 cm−1 band is a positive identification of amyloid fibrils. Sodium dodecyl sulfate micelles that solubilize and disaggregate preaggregated Aβ samples deplete the 1625 cm 1 band but do not affect the 1610 cm 1 band, demonstrating that the 1610 cm−1 band is due to very stable fibrils. We demonstrate that the 1610 cm−1 transition arises from amide I modes by mutating out the only side-chain residue that could give rise to this transition, and we explore the potential structural origins of the transition by simulating 2D IR spectra based on Aβ crystal structures. It was not previously possible to distinguish stable Aβ fibrils from the less stable β-sheet-rich oligomers with infrared light. This 2D IR signature will be useful for Alzheimer’s research on Aβ aggregation, fibril formation, and toxicity.

Self‐Assembly of an Amino Acid Derivative into an Antimicrobial Hydrogel Biomaterial

“…A minor peak at 1700 cm −1 can be assigned to the protonated COOH; this peak is more intense in the powder form, and we inferred this is due to partial deprotonation in the gel state. By contrast, the shoulder at 1623 cm −1 arises in the self‐assembled state and corresponds to the traditional signature of amyloid fibrils . The signal at 1600 cm −1 was already reported for Phe‐derived supramolecular xerogels, however, it is present also in the FTIR spectrum of N‐ (4‐nitrobenzoyl)‐Phe in its non‐assembled state, and could be due to the aromatic C=C stretching .…”

Vibrational Approach to the Dynamics and Structure of Protein Amyloids

“…The spectroscopic signatures of the stable amyloid fibrils have been also distinguished from oligomeric intermediates using more sensitive 2D-IR spectroscopy. A unique transition at 1610 cm −1 is observed in the 2D-IR spectra of the mature fibrils of both Aβ 1–40 and Aβ 1–42 [52]. This band does not appear in other Aβ aggregates including β-sheet-structure-like oligomers, and is not seen in linear IR spectroscopy because it is occluded by the broad band at ~1625 cm −1 .…”

Insight into the internal structure of amyloid-β oligomers by isotope-edited Fourier transform infrared spectroscopy

“…[45][46][47] These approximations are insufficient for nearest neighbor interactions which are therefore modeled from density functional theory calculations of small peptides. [48][49][50][51][52][53] Conformational dynamics can be accounted for either by statistical variation of the parameters, [54][55][56] by averaging spectra of snapshot structures from molecular dynamics simulations [57][58][59] or by direct time-domain approaches which also take into account motional narrowing. [60][61][62][63] The relevant model structure for this work are antiparallel b-sheets.…”