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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

Growth speed distributions of glucagon fibrils at various glucagon concentrations (displayed in top-right corners) are presented as histograms (boxes of width 10 nm/min).
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f5: Growth speed distributions of glucagon fibrils at various glucagon concentrations (displayed in top-right corners) are presented as histograms (boxes of width 10 nm/min).

Mentions: The model presented above with two competing fibril morphologies is further supported by the measurements of speeds at which the fibrils are growing (Fig. 5). The speed distributions seem to have two peaks, whose magnitudes depend on the glucagon concentration. At low glucagon concentration the dominant peak is at ~ 20–30 nm/min, which probably corresponds to the growing speed of twisted fibrils composed of glucagon monomers. On the other hand, at large glucagon concentration the dominant peak is at ~ 100 nm/min, which probably corresponds to the growing speed of non-twisted fibrils composed of glucagon trimers.


A monomer-trimer model supports intermittent glucagon fibril growth.

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

Growth speed distributions of glucagon fibrils at various glucagon concentrations (displayed in top-right corners) are presented as histograms (boxes of width 10 nm/min).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f5: Growth speed distributions of glucagon fibrils at various glucagon concentrations (displayed in top-right corners) are presented as histograms (boxes of width 10 nm/min).
Mentions: The model presented above with two competing fibril morphologies is further supported by the measurements of speeds at which the fibrils are growing (Fig. 5). The speed distributions seem to have two peaks, whose magnitudes depend on the glucagon concentration. At low glucagon concentration the dominant peak is at ~ 20–30 nm/min, which probably corresponds to the growing speed of twisted fibrils composed of glucagon monomers. On the other hand, at large glucagon concentration the dominant peak is at ~ 100 nm/min, which probably corresponds to the growing speed of non-twisted fibrils composed of glucagon trimers.

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