Direct Nanospectroscopic Verification of the Amyloid Aggregation Pathway

Angewandte Chemie
Ewelina LipiecRenato Zenobi

Abstract

The aggregation pathways of neurodegenerative peptides determine the disease etiology, and their better understanding can lead to strategies for early disease treatment. Previous research has allowed modelling of hypothetic aggregation pathways. However, their direct experimental observation has been elusive owing to methodological limitations. Herein, we demonstrate that nanoscale chemical mapping by tip-enhanced Raman spectroscopy of single amyloid fibrils at various stages of aggregation captures the fibril formation process. We identify changes in TERS/Raman marker bands for Aβ1-42 , including the amide III band (above 1255 cm-1 for turns/random coil and below 1255 cm-1 for β-sheet conformation). The spatial distribution of β-sheets in aggregates is determined, allowing verification of a particular fibrillogenesis pathway, starting from aggregation of monomers to meta-stable oligomers, which then rearrange to ordered β-sheets, already at the oligomeric or protofibrillar stage.

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Citations

Jul 13, 2019·Chembiochem : a European Journal of Chemical Biology·Stanislav Rizevsky, Dmitry Kurouski
May 20, 2020·Chemical Society Reviews·Dmitry KurouskiAndrea Centrone
Oct 31, 2018·Biosensors·Marta Maria Pereira da Silva Neves, Daniel Martín-Yerga
Mar 27, 2019·Nature Protocols·Naresh KumarAndrew J Pollard
Sep 29, 2019·Nucleic Acids Research·Ewelina LipiecWojciech M Kwiatek
Mar 14, 2020·Applied Spectroscopy·Giovanni Luca BartolomeoRenato Zenobi
Sep 24, 2020·Angewandte Chemie·Ewelina LipiecRenato Zenobi
Aug 29, 2019·ACS Chemical Neuroscience·Sreeprasad Sreenivasan, Mahesh Narayan
Jul 11, 2019·ACS Chemical Neuroscience·Sreenivasan Sreeprasad, Mahesh Narayan
Dec 19, 2021·Analytical Chemistry·Dana Cialla-MayJürgen Popp

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