TY - JOUR
T1 - Direct Nanospectroscopic Verification of the Amyloid Aggregation Pathway
AU - Lipiec, Ewelina
AU - Perez-Guaita, David
AU - Kaderli, Janina
AU - Wood, Bayden R.
AU - Zenobi, Renato
PY - 2018/7/9
Y1 - 2018/7/9
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - protein aggregation pathway
KW - secondary structure
KW - tip-enhanced Raman spectroscopy
KW - β-amyloid
UR - http://www.scopus.com/inward/record.url?scp=85049588061&partnerID=8YFLogxK
U2 - 10.1002/anie.201803234
DO - 10.1002/anie.201803234
M3 - Article
C2 - 29749066
AN - SCOPUS:85049588061
SN - 1433-7851
VL - 57
SP - 8519
EP - 8524
JO - Angewandte Chemie - International Edition
JF - Angewandte Chemie - International Edition
IS - 28
ER -