Aarhus University Seal / Aarhus Universitets segl

Daniel Otzen

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

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Department of Physics and Astronomy
  • Interdisciplinary Nanoscience Center
  • Department of Molecular Biology
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

    Research areas

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

See relations at Aarhus University Citationformats

ID: 20451625