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A monomer-trimer model supports intermittent glucagon fibril growth.

Košmrlj A, Cordsen P, Kyrsting A, Otzen DE, Oddershede LB, Jensen MH - Sci Rep (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Harvard University, Department of Physics, 17 Oxford Street, Cambridge, MA 02138, USA.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Distributions of stop (a) and growth (b) durations for fibrils grown at various glucagon concentrations.Straight lines indicate linear fits to the cumulative data. Three extremely long pauses were removed from the 3 mg/mL sample.
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f2: Distributions of stop (a) and growth (b) durations for fibrils grown at various glucagon concentrations.Straight lines indicate linear fits to the cumulative data. Three extremely long pauses were removed from the 3 mg/mL sample.

Mentions: By inspecting the time courses of fibril lengths (Fig. 1d), we find that at all glucagon concentrations the fibril growth is characterized by periods of growth (go state) interrupted by periods of stasis (stop state). The stop states are seen as plateaus, where the fibril does not elongate. As seen in our previous work16, the distributions of the stop and go event durations (displayed in Fig. 2) follow exponential distributions and are fitted to the form f(x) = a · exp(−k · t). A fibril leaves the stop state at rate ks→g given by stop durations (Fig. 2a) and go state at rate kg→s given by growth durations (Fig. 2b). Both switching rates depend on the glucagon concentration and results are summarized in Table 1.


A monomer-trimer model supports intermittent glucagon fibril growth.

Košmrlj A, Cordsen P, Kyrsting A, Otzen DE, Oddershede LB, Jensen MH - Sci Rep (2015)

Distributions of stop (a) and growth (b) durations for fibrils grown at various glucagon concentrations.Straight lines indicate linear fits to the cumulative data. Three extremely long pauses were removed from the 3 mg/mL sample.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4355668&req=5

f2: Distributions of stop (a) and growth (b) durations for fibrils grown at various glucagon concentrations.Straight lines indicate linear fits to the cumulative data. Three extremely long pauses were removed from the 3 mg/mL sample.
Mentions: By inspecting the time courses of fibril lengths (Fig. 1d), we find that at all glucagon concentrations the fibril growth is characterized by periods of growth (go state) interrupted by periods of stasis (stop state). The stop states are seen as plateaus, where the fibril does not elongate. As seen in our previous work16, the distributions of the stop and go event durations (displayed in Fig. 2) follow exponential distributions and are fitted to the form f(x) = a · exp(−k · t). A fibril leaves the stop state at rate ks→g given by stop durations (Fig. 2a) and go state at rate kg→s given by growth durations (Fig. 2b). Both switching rates depend on the glucagon concentration and results are summarized in Table 1.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Harvard University, Department of Physics, 17 Oxford Street, Cambridge, MA 02138, USA.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus