Mechanical Stress Affects Glucagon Fibrillation Kinetics and Fibril Structure

Publication: Research - peer-reviewJournal article – Annual report year: 2011

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  • Author: Macchi, Francesca

    Aarhus University, Department of Molecular Biology

  • Author: Hoffmann, Søren V.

    Aarhus University, Institute for Storage Ring Facilities, ISA

  • Author: Carlsen, Martin


  • Author: Vad, Brian

    Aarhus University, Department of Molecular Biology

  • Author: Imparato, Alberto

    Aarhus University, Department of Physics and Astronomy

  • Author: Rischel, Christian

    Novo Nordisk A/S, Protein Structure and Biophysics

  • Author: Otzen, Daniel E.

    Aarhus University, Department of Molecular Biology

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Mechanical stress can strongly influence the capability of a protein to aggregate and the kinetics of aggregation, but there is little insight into the underlying mechanism. Here we study the effect of different mechanical stress conditions on the fibrillation of the peptide hormone glucagon, which forms different fibrils depending on temperature, pH, ionic strength, and concentration. A combination of spectroscopic and microscopic data shows that fibrillar polymorphism can also be induced by mechanical stress. We observed two classes of fibrils: a low-stress and a high-stress class, which differ in their kinetic profiles, secondary structure as well as morphology and that are able to self-propagate in a template-dependent fashion. The bending rigidity of the low-stress fibrils is sensitive to the degree of mechanical perturbation. We propose a fibrillation model, where interfaces play a fundamental role in the switch between the two fibrillar classes. Our work also raises the cautionary note that mechanical perturbation is a potential source of variability in the study of fibrillation mechanisms and fibril structures.
Original languageEnglish
Publication date2011
Journal number20
CitationsWeb of Science® Times Cited: 3
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ID: 6441357