Fast Probing Amyloid Polymorphism via Nanopore Translocation
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Date
2023-11-08
Publication Type
Journal Article
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yes
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Abstract
Neurodegenerative diseases are characterized by the presence of cross-β-sheet amyloid fibrils and a rich mesoscopic polymorphism, requiring noninvasive detection with high fidelity. Here, we introduce a methodology that can probe via a sensitive synthetic nanopore the complex polymorphism of amyloid fibrils by an automated and fast screening protocol. Statistically analyzing the translocation events on two model amyloid systems derived from β-lactoglobulin and lysozyme allows extracting the cross-sectional configuration of hydrated amyloid fibrils from current block amplitude and correlating dwell time with fibril length. These findings are consistent with the amyloid polymorphs observed in solution by atomic force microscopy. Furthermore, the ionic current signal of a single translocation event can reveal abnormally aggregated conformations of amyloid fibrils without potential artifacts associated with microscopy methods. This study introduces an effective approach to physically discriminating and separating amyloid and may serve in the rapid diagnosis of early aggregating pathological amyloidosis.
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published
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Journal / series
Volume
23 (21)
Pages / Article No.
9912 - 9919
Publisher
American Chemical Society
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Subject
amyloid; polymorphism; nanopore; β-lactoglobulin; lysozyme; Confirmation; Monomers; Nanofibers; Nanopores; Peptides and proteins
Organisational unit
03857 - Mezzenga, Raffaele / Mezzenga, Raffaele