A Fluorescent Sensor for Quantitative Super-Resolution Imaging of Amyloid Fibril Assembly**

Amandeep Kaur, Liam D. Adair, Sarah R. Ball, Elizabeth J. New, Margaret Sunde

Research output: Contribution to journalArticleResearchpeer-review

3 Citations (Scopus)

Abstract

Many soluble proteins can self-assemble into macromolecular structures called amyloids, a subset of which are implicated in a range of neurodegenerative disorders. The nanoscale size and structural heterogeneity of prefibrillar and early aggregates, as well as mature amyloid fibrils, pose significant challenges for the quantification of amyloid morphologies. We report a fluorescent amyloid sensor AmyBlink-1 and its application in super-resolution imaging of amyloid structures. AmyBlink-1 exhibits a 5-fold increase in ratio of the green (thioflavin T) to red (Alexa Fluor 647) emission intensities upon interaction with amyloid fibrils. Using AmyBlink-1, we performed nanoscale imaging of four different types of amyloid fibrils, achieving a resolution of ≈30 nm. AmyBlink-1 enables nanoscale visualization and subsequent quantification of morphological features, such as the length and skew of individual amyloid aggregates formed at different times along the amyloid assembly pathway.

Original languageEnglish
Article numbere202112832
Number of pages6
JournalAngewandte Chemie - International Edition
Volume61
Issue number10
DOIs
Publication statusPublished - 1 Mar 2022
Externally publishedYes

Keywords

  • Amyloid
  • Fluorescence
  • Oligomers
  • Sensor
  • Super-resolution

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