Abstract
Amyloid fibrils are composed of aggregated peptides or proteins in a fibrillar structure with a higher β-sheet content than in their native structure. To characterize them, we used an innovative tool that coupled infrared spectroscopy with atomic force microscopy (AFM-IR). With this method, we show that we can detect different individual aggregated species from oligomers to fibrils and study their morphologies by AFM and their secondary structures based on their IR spectra. AFM-IR overcomes the weak spatial resolution of usual infrared spectroscopy and achieves a resolution of ten nanometers, the size of isolated fibrils. We characterized oligomers, amyloid fibrils of Aβ42 and fibrils of α-synuclein. To our surprise, we figured out that the nature of some surfaces (ZnSe) used to study the samples induces destructuring of amyloid samples, leading to amorphous aggregates. We strongly suggest taking this into consideration in future experiments with amyloid fibrils. More importantly, we demonstrate the advantages of AFM-IR, with a high spatial resolution (≤ 10 nm) allowing spectrum recording on individual aggregated supramolecular entities selected thanks to the AFM images or on thin layers of proteins.
Highlights
Alzheimer’s disease (AD) is the most prevalent form of neurodegenerative dementia and affects more than 50 million patients worldwide
Our goal is to study the differences in conformations between protein aggregates by atomic force microscopy (AFM)-IR and to confirm that spectra obtained by this recent method are comparable with those collected with attenuated total reflection (ATR)-FTIR
The aggregation kinetics of Aβ42 peptide are characterized by a lag phase, containing mainly monomers and oligomers, followed by a rapid increase in amyloid fibrils formation until a plateau where all or most Aβ42 is in a fibrillar form
Summary
Alzheimer’s disease (AD) is the most prevalent form of neurodegenerative dementia and affects more than 50 million patients worldwide. This number will double every 20 years to reach > 150 million of cases around 2050 [1]. One of the characteristic histopathological markers of AD is the presence of proteinaceous deposits in the brains of patients, amyloid plaques localized outside neurons, and synaptic connections [2,3] and intraneuronal neurofibrillary tangles containing hyperphosphorylated Tau protein [4]. 39-to-43-residue misfolded peptide, the amyloid β peptide (Aβ). This peptide is a cleavage product of the amyloid precursor protein (APP) a membrane protein [5,6]. Aβ40 and Aβ42 are the main components of amyloid plaques [7]
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