Illuminating amyloid fibrils: Fluorescence-based single-molecule approaches

Rice, Lauren J.; Ecroyd, Heath; Oijen, Antoine M. van

doi:10.1016/j.csbj.2021.08.017

Cited by 12 publications

(11 citation statements)

References 219 publications

(315 reference statements)

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“…The other single molecule fluorescent super-resolution imaging technique is total internal reflection fluorescence microscopy (TIRF M), which helps to investigate the dynamic process associated with amyloid fibril formation. 105 The technical input of this microscopy technique is to direct a laser beam of excitation into a liquid−solid interface at such an angle that the light will be completely internally reflected (Figure 5b). This condition generates an evanescent wave at the interface, which decreases in space, thereby enabling the restricted imaging within a certain region in space, typically by 100 nm.…”

Section: Interaction Of Single Amino Acid-based Fibrils With Lipid Ve...mentioning

confidence: 99%

“…Photobleaching of covalently attached probe molecules provides the profile of step bleaching, which accounts for the number of subunits present in the proteins or fibrils (Figure 5c). 105 Although this technique has recently been extensively used in a number of protein fibrils, their application seems to be limited to single amino acid-based fibrils. This opens the possibility for researchers to search for the structural integrity of single amino acid-based amyloid fibrils.…”

Section: Interaction Of Single Amino Acid-based Fibrils With Lipid Ve...mentioning

confidence: 99%

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Interactions between Lipid Vesicle Membranes and Single Amino Acid Fibrils: Probable Origin of Specific Neurological Disorders

Nandi,

Sarkar

2024

Langmuir

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Amyloid fibrils are known to be responsible for several neurological disorders, like Alzheimer's disease (AD), Parkinson's disease (PD), etc. For decades, mostly proteins and peptide-based amyloid fibrils have been focused on, and the topic has acknowledged the rise, development, understanding of, and controversy, as well. However, the single amino acid based amyloid fibrils, responsible for several disorders, such as phenylketonuria, tyrosenimia type II, hypermethioninemia, etc., have gotten scientific attention lately. To understand the molecular level pathogenesis of such disorders originated due to the accumulation of single amino acid-based amyloid fibrils, interaction of these fibrils with phospholipid vesicle membranes is found to be an excellent cell-free in vitro setup. Based on such an in vitro setup, these fibrils show a generic mechanism of membrane insertion driven by electrostatic and hydrophobic effects inside the membrane that reduces the integral rigidity of the membrane. Alteration of such fundamental properties of the membrane, therefore, might be referred to as one of the prime pathological factors for the development of these neurological disorders. Hence, such interactions must be investigated in cellular and intracellular compartments to design suitable therapeutic modulators against fibrils.

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Section: Interaction Of Single Amino Acid-based Fibrils With Lipid Ve...mentioning

confidence: 99%

Section: Interaction Of Single Amino Acid-based Fibrils With Lipid Ve...mentioning

confidence: 99%

Interactions between Lipid Vesicle Membranes and Single Amino Acid Fibrils: Probable Origin of Specific Neurological Disorders

Nandi,

Sarkar

2024

Langmuir

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“…First suggested by negative-staining and scanning TEM ( Wischik et al, 1988 ), the structurally variable regions of tau fibrils largely escape further structural characterization by cryo-EM or ssNMR ( Andronesi et al, 2008 ). They can still be addressed by ensemble-based methods such as solution-state NMR ( Sillen et al, 2005 ; Bibow et al, 2011 ; Lippens et al, 2016 ) as well as fluorescence-based single-molecule approaches that enables dissecting low-populated, transient states that form during the amyloid assembly including oligomers or secondary nucleation processes ( Kundel et al, 2018a ; Kundel et al, 2018b ; Kjaergaard et al, 2018 ; Rice et al, 2021 ; Yang et al, 2021 ). These structurally dynamic, disordered regions yet deserve particular attention as they can play a regulatory role in amyloid fibril formation especially through their abundant and diverse PTMs including truncations ( Morris et al, 2015 ; Despres et al, 2017 ).…”

Section: Assembly Properties and Propagation Of Amyloid Fibrils In Ne...mentioning

confidence: 99%

Deciphering the Structure and Formation of Amyloids in Neurodegenerative Diseases With Chemical Biology Tools

et al. 2022

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Protein aggregation into highly ordered, regularly repeated cross-β sheet structures called amyloid fibrils is closely associated to human disorders such as neurodegenerative diseases including Alzheimer’s and Parkinson’s diseases, or systemic diseases like type II diabetes. Yet, in some cases, such as the HET-s prion, amyloids have biological functions. High-resolution structures of amyloids fibrils from cryo-electron microscopy have very recently highlighted their ultrastructural organization and polymorphisms. However, the molecular mechanisms and the role of co-factors (posttranslational modifications, non-proteinaceous components and other proteins) acting on the fibril formation are still poorly understood. Whether amyloid fibrils play a toxic or protective role in the pathogenesis of neurodegenerative diseases remains to be elucidated. Furthermore, such aberrant protein-protein interactions challenge the search of small-molecule drugs or immunotherapy approaches targeting amyloid formation. In this review, we describe how chemical biology tools contribute to new insights on the mode of action of amyloidogenic proteins and peptides, defining their structural signature and aggregation pathways by capturing their molecular details and conformational heterogeneity. Challenging the imagination of scientists, this constantly expanding field provides crucial tools to unravel mechanistic detail of amyloid formation such as semisynthetic proteins and small-molecule sensors of conformational changes and/or aggregation. Protein engineering methods and bioorthogonal chemistry for the introduction of protein chemical modifications are additional fruitful strategies to tackle the challenge of understanding amyloid formation.

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“…Studying the aggregation process of amyloid peptides in detail is a challenging task especially at concentrations in the order of magnitude of physiological ones. For that, the use of selective and sensitive detection methods such as fluorescence-based ones is highly desirable to study peptides at lower concentrations [5]. This strategy implies a modification of the peptide structure by adding a label often on its N-terminal end.…”

Section: Introductionmentioning

confidence: 99%

Taylor dispersion analysis discloses the impairment of Aβ peptide aggregation by the presence of a fluorescent tag

et al. 2022

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The use of fluorescently tagged amyloid peptides, implicated in Alzheimer's disease, to study their aggregation at low concentrations is a common method; however, the fluorescent tag should not introduce a bias in the aggregation process. In this work, native amyloid peptides Aβ(1–40) and Aβ(1–42) and fluorescein‐5‐isothiocyanate (FITC), tagged ones, were studied using Taylor dispersion analysis coupled with a simultaneous UV and light‐emitting diode‐induced fluorescence detection, to unravel the effect of FITC on the aggregation process. For that, a total concentration of 100 µM of peptides consisting of a mixture of native and tagged ones (up to 10% in moles) was applied. Results demonstrated that FITC had a strong inhibition effect upon the aggregation behaviour of Aβ(1–42), whereas for Aβ(1–40), only a retardation in kinetics was observed. It was also shown that when mixed solutions of Aβ(1–40) and Aβ(1–42) are used, the Aβ(1–42) alloform was the leading peptide in the aggregation process, and when the latter was tagged, the aggregation kinetics decreased but the lifetime of potentially toxic oligomers was drastically increased. These results confirmed that the hydrophilicity of the N‐terminus part of the peptide plays a major role in the aggregation process.

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Illuminating amyloid fibrils: Fluorescence-based single-molecule approaches

Abstract: Graphical abstract

Cited by 12 publications

References 219 publications

Interactions between Lipid Vesicle Membranes and Single Amino Acid Fibrils: Probable Origin of Specific Neurological Disorders

Interactions between Lipid Vesicle Membranes and Single Amino Acid Fibrils: Probable Origin of Specific Neurological Disorders

Deciphering the Structure and Formation of Amyloids in Neurodegenerative Diseases With Chemical Biology Tools

Taylor dispersion analysis discloses the impairment of Aβ peptide aggregation by the presence of a fluorescent tag

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