Long-term, super-resolution imaging of amyloid structures using transient amyloid binding microscopy

Tianben Ding, Kevin Spehar, Jan Bieschke, Matthew D. Lew

Research output: Chapter in Book/Report/Conference proceedingConference contributionpeer-review

5 Scopus citations

Abstract

Amyloid fibrils and tangles are signatures of Alzheimer disease, but nanometer-sized aggregation intermediates are hypothesized to be the structures most toxic to neurons. The structures of these oligomers are too small to be resolved by conventional light microscopy. We have developed a simple and versatile method, called transient amyloid binding (TAB), to image amyloid structures with nanoscale resolution using amyloidophilic dyes, such as Thioflavin T, without the need for covalent labeling or immunostaining of the amyloid protein. Transient binding of ThT molecules to amyloid structures over time generates photon bursts that are used to localize single fluorophores with nanometer precision. Continuous replenishment of fluorophores from the surrounding solution minimizes photobleaching, allowing us to visualize a single amyloid structure for hours to days. We show that TAB microscopy can image both the oligomeric and fibrillar stages of amyloid-β aggregation. We also demonstrate that TAB microscopy can image the structural remodeling of amyloid fibrils by epi-gallocatechin gallate. Finally, we utilize TAB imaging to observe the non-linear growth of amyloid fibrils.

Original languageEnglish
Title of host publicationSingle Molecule Spectroscopy and Superresolution Imaging XII
EditorsFelix Koberling, Zygmunt K. Gryczynski, Ingo Gregor
PublisherSPIE
ISBN (Electronic)9781510624108
DOIs
StatePublished - 2019
EventSingle Molecule Spectroscopy and Superresolution Imaging XII 2019 - San Francisco, United States
Duration: Feb 2 2019Feb 3 2019

Publication series

NameProgress in Biomedical Optics and Imaging - Proceedings of SPIE
Volume10884
ISSN (Print)1605-7422

Conference

ConferenceSingle Molecule Spectroscopy and Superresolution Imaging XII 2019
Country/TerritoryUnited States
CitySan Francisco
Period02/2/1902/3/19

Keywords

  • Amyloid aggregation
  • Amyloid-beta peptides
  • Bindingactivated fluorescence
  • Single-molecule localization microscopy

Fingerprint

Dive into the research topics of 'Long-term, super-resolution imaging of amyloid structures using transient amyloid binding microscopy'. Together they form a unique fingerprint.

Cite this