Biomedical Engineering Reference
In-Depth Information
Fig. 9
Influence of peptide concentration on aggregation kinetics. (
Left
) Effect of concentration on
the lag phase time t
50
(
a
) and elongation rate (
b
) for low and high values (dE
D
2:5 kcal/mol,
black circles
; dE
D
0:0 kcal/mol,
green squares
, respectively) of the amyloidogenic tendency.
The symbols represent the average value calculated from 15 simulations for dE
D
2:5 kcal/mol
and 10 simulations for dE
D
0:0 kcal/mol. The error bars represent the minimum and the
maximum values. The
vertical dotted line
indicates the critical concentration of micelle formation.
(
Right
) Influence of the initial monomeric concentration on the kinetics of insulin fibril formation
as measured by Thioflavin T fluorescence [
57
]. Note that the higher the concentration of
monomeric insulin is at the beginning of the experiments, the shorter is the lag phase and the
faster is the elongation rate. Reprinted from [
37
](
left
)and[
57
](
right
) with permission by Elsevier
(
left
) and American Chemical Society (
right
)
even within the same sample, a number of coexisting morphologies can be
detected. [
59
,
63
] Recently, it was observed that the CGF peptide model is able
to generate fibrils with distinct morphologies. [
64
] Interestingly, the populations of
the different morphologies are strongly and nontrivially influenced by the amyloido-
genic propensity dE, and two main mechanisms for fibril morphogenesis emerge.
When the CGF peptide is highly prone to aggregate (dE
2.0 kcal/mol),
the morphogenesis is under thermodynamic control, meaning that the morphology
with the highest stability will emerge with the highest probability. In contrast, when
the CGF peptide has a low amyloidogenic tendency (dE
D
1:5,
2.5 kcal/mol),
the fibril morphogenesis is under kinetic control. The morphologies that nucleate
D
2:25,
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