Quartz crystal microbalance studies of multilayer glucagon fibrillation at the solid-liquid interface

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    Abstract

    We have used a quartz crystal microbalance with dissipation (QCM-D) to monitor the changes in layer thickness and viscoelastic properties accompanying multilayer amyloid deposition in situ for the first time. By means of atomic force microscope imaging, an unequivocal correlation is established between the interfacial nucleation and growth of glucagon fibrils and the QCM-D response. The combination of the two techniques allows us to study the temporal evolution of the interfacial fibrillation process. We have modeled the QCM-D data using an extension to the Kelvin-Voigt viscoelastic model. Three phases were observed in the fibrillation process: 1), a rigid multilayer of glucagon monomers forms and slowly rearranges; 2), this multilayer subsequently evolves into a dramatically more viscoelastic layer, containing a polymorphic network of micrometer-long fibrils growing from multiple nucleation sites; and 3), the fibrillar formation effectively stops as a result of the depletion of bulk-phase monomers, although the process can be continued without a lag phase by subsequent addition of fresh monomers. The robustness of the QCM-D technique, consolidated by complementary atomic force microscope studies, should make it possible to combine different components thought to be involved in the plaque formation process and thus build up realistic models of amyloid plaque formation in vitro.
    Original languageEnglish
    JournalBiophysical Journal
    Volume93
    Issue6
    Pages (from-to)2162-9
    Number of pages7
    ISSN0006-3495
    DOIs
    Publication statusPublished - 2007

    Keywords

    • Biophysical Phenomena
    • Biophysics
    • Biosensing Techniques
    • Electrochemistry
    • Glucagon
    • Microscopy, Atomic Force
    • Multiprotein Complexes
    • Quartz
    • Thermodynamics

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