Issue 23, 2014

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

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

Supplementary files

Article information

Article type
Paper
Submitted
14 Feb 2014
Accepted
02 Apr 2014
First published
25 Apr 2014

Soft Matter, 2014,10, 4162-4172

Author version available

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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