A monomer-trimer model supports intermittent glucagon fibril growth

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  • Andrej Košmrlj, Harvard University, Department of Physics, USA
  • Pia Cordsen, Copenhagen University, Niels Bohr Institute, CMOL, Danmark
  • Anders Kyrsting, Copenhagen University, Niels Bohr Institute, CMOL, Danmark
  • Daniel Otzen
  • Lene B Oddershede, Copenhagen University, Niels Bohr Institute, CMOL, Danmark
  • Mogens H Jensen, Copenhagen University, Niels Bohr Institute, CMOL, Danmark

We investigate in vitro fibrillation kinetics of the hormone peptide glucagon at various concentrations using confocal microscopy and determine the glucagon fibril persistence length 60μm. At all concentrations we observe that periods of individual fibril growth are interrupted by periods of stasis. The growth probability is large at high and low concentrations and is reduced for intermediate glucagon concentrations. To explain this behavior we propose a simple model, where fibrils come in two forms, one built entirely from glucagon monomers and one entirely from glucagon trimers. The opposite building blocks act as fibril growth blockers, and this generic model reproduces experimental behavior well.

OriginalsprogEngelsk
Artikelnummer9005
TidsskriftScientific Reports
Vol/bind5
Sider (fra-til)1-6
Antal sider6
ISSN2045-2322
DOI
StatusUdgivet - 11 mar. 2015

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