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Volume 12 Issue 5, May 2020

Determining dynamics during amyloid assembly

Alzheimer's disease is linked to the self-assembly of Aß42 peptides into misfolded fibrillar aggregates. Now, a team led by Michele Vendruscolo, Sara Linse and Tuomas Knowles have obtained direct measurements of the dynamic self-assembly and disassembly of Aß42 peptide oligomers, as well as their subsequent conversion into amyloid fibrils. These findings show that although all mature amyloid fibrils must originate from oligomers, most Aß42 oligomers dissociate back to their monomeric precursors without forming new fibrils. The cover image depicts a schematic representation of the nucleation of peptide aggregates and the dynamics of peptide assembly and disassembly during the formation of an amyloid fibril.

See Michaels et al

IMAGE: Nicola De Mitri and Claudia Flandoli. COVER DESIGN: Tulsi Voralia


  • Bruce C. Gibb takes a look at the chemistry and biochemistry of intermittent fasting.

    • Bruce C. Gibb


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News & Views

  • A balance between order and disorder provides living materials with just the right amount of disorder needed to sustain life. This feature is currently not found in synthetic materials. Now, a route to the production of composite membranes that are simultaneously stiff and reconfigurable upon contact has been developed.

    • Ankit Jain
    • Rein V. Ulijn
    News & Views
  • Single-molecule magnets are able to store information through their magnetic anisotropy, making them very promising systems for memory applications. Now, femtosecond-laser-initiated molecular dynamics that modulate magnetic anisotropy have been observed, paving the way for operation on ultrafast timescales.

    • Eric Collet
    News & Views
  • A series of mesoscale supramolecular hexagonal grids have been constructed in solution through stepwise intra- then intermolecular coordination-driven self-assembly, and characterized with atomic resolution by scanning tunnelling microscopy and spectroscopy.

    • Ruoning Li
    • Yongfeng Wang
    News & Views
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Review Articles

  • Cyclic polymers have a ring-like architecture and one of the most important consequences of this topology is the absence of any chain ends, which typically have a substantial impact on the physical properties of macromolecules. This Review Article discusses advances in the synthesis, purification and characterization of cyclic polymers and the potential applications they may prove useful for.

    • Farihah M. Haque
    • Scott M. Grayson
    Review Article
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  • Aβ42 oligomers are key toxic species associated with protein aggregation; however, the molecular pathways determining the dynamics of oligomer populations have remained unknown. Now, direct measurements of oligomer populations, coupled to theory and computer simulations, define and quantify the dynamics of Aβ42 oligomers formed during amyloid aggregation.

    • Thomas C. T. Michaels
    • Andela Šarić
    • Tuomas P. J. Knowles
  • Controlling single-molecule magnets (SMMs) with ultrashort laser pulses could be key to future data storage devices, however, the photophysics of SMMs is complex. Now, using a monomer model system, it has been shown that optical excitation of Mn(iii)-SMMs leads to a modulation of the Jahn–Teller distortion, which is important for its magnetic anisotropy.

    • Florian Liedy
    • Julien Eng
    • J. Olof Johansson
  • Despite the importance of trifluoromethylated compounds, direct catalytic methods for the conversion of C(sp3)–H bonds into the corresponding C(sp3)–CF3 analogues have remained elusive. This transformation has now been achieved by the merger of copper catalysis with decatungstate photocatalysis, enabling the C(sp3)–H trifluoromethylation of abundant feedstocks, natural products and pharmaceuticals.

    • Patrick J. Sarver
    • Vlad Bacauanu
    • David W. C. MacMillan
  • Metal-mediated self-assembly in solution typically leads to small two- and three-dimensional architectures on scales smaller than 10 nm, but now a series of large, discrete, two-dimensional supramolecular hexagonal grids have been prepared through a combination of intra- and intermolecular coordination interactions. These 20-nm-wide grids have been imaged at submolecular resolution using scanning tunnelling microscopy.

    • Zhe Zhang
    • Yiming Li
    • Xiaopeng Li
  • Even- and odd-numbered homologues of some hydrocarbons are known to exhibit different trends in solid-state properties. Now, experimental and computational investigations on a homologous series of a stereochemically well-defined hydrocarbon have revealed an odd–even effect in conformational behaviour in solution that is caused by a single gauche interaction.

    • Johan A. Pradeilles
    • Siying Zhong
    • Varinder K. Aggarwal
  • Single-molecule nanopore measurements have revealed ligand-induced conformational changes in the catalytic cycle of dihydrofolate reductase, and showed that the enzyme adopts distinctive conformers, which have different affinities for substrates and products. Crossing the transition state facilitates conformer exchange, suggesting that the chemical step catalyses the switch between conformers to obtain a more efficient product release.

    • Nicole Stéphanie Galenkamp
    • Annemie Biesemans
    • Giovanni Maglia
  • A catalytic para-selective alkylation reaction connects C–H functionalization and decarboxylative coupling strategies using simple bases to trap a previously hidden intermediate. This reaction exploits an ‘inverted sequence’ that forms the C–C bond prior to C–H bond cleavage and provides a new entry into C–H functionalization reactions.

    • Francisco de Azambuja
    • Ming-Hsiu Yang
    • Ryan A. Altman
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Amendments & Corrections

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