A Fluorescent Sensor for Quantitative Super‐Resolution Imaging of Amyloid Fibril Assembly. (20th January 2022)

• Record Type: Journal Article
• Authors: Kaur, Amandeep; Adair, Liam D.; Ball, Sarah R.; New, Elizabeth J.; Sunde, Margaret
• Is Part Of: Angewandte Chemie. Volume 134:Number 10(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-01-20
• Subjects: Amyloid -- Fluorescence -- Oligomers -- Sensor -- Super-resolution; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.202112832
• Languages: English
• ISSNs: 0044-8249

Abstract

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. Abstract : Applicable in single‐molecule localization microscopy, AmyBlink‐1 facilitates nanoscale imaging of a range of amyloid fibrils, achieving a resolution of 30 nm. Cluster‐detection analyses of the super‐resolution images enable the quantification of the nanoscale morphological features of intermediates formed at different times in the amyloid assembly cascade.