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Issue 23, 2014
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Mapping amyloid-β(16-22) nucleation pathways using fluorescence lifetime imaging microscopy

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Abstract

The cross-β peptide architecture is associated with numerous functional biomaterials and deleterious disease related aggregates. While these diverse and ubiquitous paracrystalline assemblies have been widely studied, a fundamental understanding of the nucleation and aggregation pathways to these structures remains elusive. Here we highlight a novel application of fluorescence lifetime imaging microscopy in characterising the critical stages of peptide aggregation. Using the central nucleating core of the amyloid-β (Aβ), Aβ(16-22), as a model cross-β system, and utilising a small fraction of rhodamine labelled peptide (Rh110-Aβ(17-22)), we map out a folding pathway from monomer to paracrystalline nanotube. Using this intrinsic fluorescence reporter, we demonstrate the effects of interfaces and evaporation on the nucleation of sub-critical concentration solutions, providing access to previously uncharacterised intermediate morphologies. Using fluorescence lifetime we follow the local peptide environment through the stages of nucleation and hydrophobic collapse, ending in a stable final structure. This work provides a metric for future implementations of measuring fluorescence lifetimes of intrinsic fluorescence reporters during the very dynamic processes relating to peptide nucleation and maturation.

Graphical abstract: Mapping amyloid-β(16-22) nucleation pathways using fluorescence lifetime imaging microscopy

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Publication details

The article was received on 14 Feb 2014, accepted on 02 Apr 2014 and first published on 25 Apr 2014


Article type: Paper
DOI: 10.1039/C4SM00361F
Author version available: Download Author version (PDF)
Citation: Soft Matter, 2014,10, 4162-4172
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    Mapping amyloid-β(16-22) nucleation pathways using fluorescence lifetime imaging microscopy

    N. R. Anthony, A. K. Mehta, D. G. Lynn and K. M. Berland, Soft Matter, 2014, 10, 4162
    DOI: 10.1039/C4SM00361F

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