Intrinsic Fluorescence of Metabolite Amyloids Allows Label‐Free Monitoring of Their Formation and Dynamics in Live Cells

• Published in: Angewandte Chemie International Edition 2018-09, Vol.57 (38), p.12444-12447
• Main Authors: Shaham‐Niv, Shira, Arnon, Zohar A., Sade, Dorin, Lichtenstein, Alexandra, Shirshin, Evgeny A., Kolusheva, Sofiya, Gazit, Ehud
• Format: Article
• Language: English
• Subjects: Amyloid; Apoptosis; Assemblies; Cellular structure; Chromophores; Fluorescence; Inborn errors of metabolism; Labeling; live cell imaging; Metabolism; Metabolites; Proteins; self-assembly
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201806565

The formation of apoptosis‐inducing amyloidal structures by metabolites has significantly extended the “amyloid hypothesis” to include non‐proteinaceous, single metabolite building blocks. However, detection of metabolite assemblies is restricted compared to their larger protein‐based counterparts owing to the hindrance of external labelling and limited immunohistochemical detection tools. Herein, we present the detection of the formation, dynamics, and cellular distribution of metabolite amyloid‐like structures and provide mechanistic insights into the generation of supramolecular chromophores. Moreover, the intrinsic fluorescence properties allow the detection of metabolite assemblies in living cells without the use of external dyes. Altogether, this intrinsic fluorescence of metabolite assemblies further verifies their amyloidal nature, while providing an important tool for further investigation of their pathological role in inborn error of metabolism disorders. Fluorescent amyloids: The detection of the formation, dynamics, and cellular distribution of metabolite amyloid‐like structures is demonstrated, leading to mechanistic insights into the generation of supramolecular chromophores. Moreover, the intrinsic fluorescence properties of the structures allow the detection of metabolite assemblies in living cells without the use of external dyes.