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Ultrasonic force microscopy for nanomechanical characterization of early and late-stage amyloid-β peptide aggregation

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Ultrasonic force microscopy for nanomechanical characterization of early and late-stage amyloid-β peptide aggregation. / Tinker-Mill, Claire; Mayes, Jennifer; Allsop, David; Kolosov, Oleg.

In: Scientific Reports, Vol. 4, 4004, 2014.

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@article{8285fd5a952042389f136083f27d66e2,
title = "Ultrasonic force microscopy for nanomechanical characterization of early and late-stage amyloid-β peptide aggregation",
abstract = "The aggregation of amyloid-β peptides into protein fibres is one of the main neuropathological features of Alzheimer{\textquoteright}s disease (AD). While imaging of amyloid-β aggregate morphology in vitro is extremely important for understanding AD pathology and development of aggregation inhibitors, unfortunately, potentially highly toxic early aggregates are difficult to observe by current electron microscopy and atomic force microscopy (AFM) methods due to low contrast and variability of peptide attachment to the substrate. Here, we use poly-L-Lysine (PLL) surface that captures all protein components from monomers to fully formed fibres, followed by nanomechanical mapping via Ultrasonic Force Microscopy (UFM), which marries high spatial resolution and nanomechanical contrast with non-destructive nature of tapping mode AFM. For the main putative AD pathogenic component, Aβ1-42, the PLL-UFM approach reveals the morphology of oligomers, protofibrils and mature fibres, and finds that a fraction of small oligomers is still present at later stages of fibril assembly.",
keywords = "Nanoscale biophysics, Scanning probe microscopy , Molecular imaging, Alzheimer's disease",
author = "Claire Tinker-Mill and Jennifer Mayes and David Allsop and Oleg Kolosov",
year = "2014",
doi = "10.1038/srep04004",
language = "English",
volume = "4",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

}

RIS

TY - JOUR

T1 - Ultrasonic force microscopy for nanomechanical characterization of early and late-stage amyloid-β peptide aggregation

AU - Tinker-Mill, Claire

AU - Mayes, Jennifer

AU - Allsop, David

AU - Kolosov, Oleg

PY - 2014

Y1 - 2014

N2 - The aggregation of amyloid-β peptides into protein fibres is one of the main neuropathological features of Alzheimer’s disease (AD). While imaging of amyloid-β aggregate morphology in vitro is extremely important for understanding AD pathology and development of aggregation inhibitors, unfortunately, potentially highly toxic early aggregates are difficult to observe by current electron microscopy and atomic force microscopy (AFM) methods due to low contrast and variability of peptide attachment to the substrate. Here, we use poly-L-Lysine (PLL) surface that captures all protein components from monomers to fully formed fibres, followed by nanomechanical mapping via Ultrasonic Force Microscopy (UFM), which marries high spatial resolution and nanomechanical contrast with non-destructive nature of tapping mode AFM. For the main putative AD pathogenic component, Aβ1-42, the PLL-UFM approach reveals the morphology of oligomers, protofibrils and mature fibres, and finds that a fraction of small oligomers is still present at later stages of fibril assembly.

AB - The aggregation of amyloid-β peptides into protein fibres is one of the main neuropathological features of Alzheimer’s disease (AD). While imaging of amyloid-β aggregate morphology in vitro is extremely important for understanding AD pathology and development of aggregation inhibitors, unfortunately, potentially highly toxic early aggregates are difficult to observe by current electron microscopy and atomic force microscopy (AFM) methods due to low contrast and variability of peptide attachment to the substrate. Here, we use poly-L-Lysine (PLL) surface that captures all protein components from monomers to fully formed fibres, followed by nanomechanical mapping via Ultrasonic Force Microscopy (UFM), which marries high spatial resolution and nanomechanical contrast with non-destructive nature of tapping mode AFM. For the main putative AD pathogenic component, Aβ1-42, the PLL-UFM approach reveals the morphology of oligomers, protofibrils and mature fibres, and finds that a fraction of small oligomers is still present at later stages of fibril assembly.

KW - Nanoscale biophysics

KW - Scanning probe microscopy

KW - Molecular imaging

KW - Alzheimer's disease

U2 - 10.1038/srep04004

DO - 10.1038/srep04004

M3 - Journal article

VL - 4

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 4004

ER -