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

Abstract

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.

Half a century of amyloids: past, present and future

“…342 It has recently been established that metabolite amyloids also possess such fluorescence properties, which also allow their detection in live cells. 343 The observed fluorescence of the fluorescence in the context of hydrogen bond networks is also in line with the crystal structure of phenylalanine in its zwitterionic form at neutral pH, as was determined by synchrotron X-ray crystallography in 2014. 344 The structure shows a network of hydrogen bonds and p-p interactions, layered with remarkably similar morphology and zig-zag arrangement as compared to protein b-sheet structures.…”

Coassembly of Complementary Peptide Nucleic Acid into Crystalline Structures by Microfluidics

“…However, the underlying mechanism which drives the autofluorescence of such supramolecular crystals is still not fully understood. [26,27] Fluorescence images of the structures were taken using different excitation and emission wavelengths showing a broad range of fluorescence over the visible region (Figure 4a-e). To examine the REES in further detail, the fluorescence spectra of dried GG and CC cocrystals were measured using a Horiba Jobin Yvon Fluoromax-4 Spectrofluorometer.…”

“…This phenomenon is defined as a shift in the emission peak toward the red edge of the electromagnetic spectrum as a result of increasing the excitation wavelength. However, the underlying mechanism which drives the autofluorescence of such supramolecular crystals is still not fully understood . Fluorescence images of the structures were taken using different excitation and emission wavelengths showing a broad range of fluorescence over the visible region ( Figure a–e).…”

Solvent‐Controlled Topological Evolution from Nanospheres to Superhelices

“…[5][6][7] To mimic these natural fibrillation process, extensive nanofibers have been developed via molecular self-assembly, [8][9][10][11] and closely related applications in the fields of optoelectronics, catalysis, biomedicine, cell culture, and artificial photosynthesis are established. [12][13][14][15][16] However, these works mainly focused on the final architectures, and the morphological evolution is rarely investigated partially owing to their fast thermodynamic equilibrium and kinetically metastable intermediates. [17] More importantly, the chirality elements on a molecular or supramolecular scale, another dramatic characteristic in organisms, are normally absent among the related researches, [18,19] thus imposing restrictions to mimic the complete and real transition processes occurring within peptide and protein fibrosis.…”