Biomedical Engineering Reference
In-Depth Information
Fig. 11
Comparison of CGF model simulations and experimental data on fibril formation in the
presence of lipid vesicles. (
Left
) Simulation results. (
Left
,
top
) Influence of peptide amyloido-
genicity on fibril growth kinetics and vesicle leakage. A single parameter, the energy difference
between amyloid-competent and amyloid-protected conformations of the peptides, is varied in
different simulations to tune amyloidogenicity. Time series of the average number of ordered polar
contacts between monomers (corresponding to the degree of fibrillation). (
Left
,
bottom
)Average
number of probes inside the vesicle, in the absence (
black
) or presence (colors) of peptides, and for
simulations where a preformed fibril was used instead of dispersed peptides. (
Right
) Experimental
data: Effect of human islet amyloid polypeptide (hIAPP) fibril growth on membrane leakage. [
69
]
Thioflavin T fluorescence intensity (
Right
,
top
) and induced membrane leakage (
Right
,
bottom
)of
three hIAPP samples (
black curves
), together with representative traces for mouse IAPP variant
which is known to be non-toxic (
gray lines
) and preformed hIAPP fibrils (
dashed lines
)areshown.
The
two vertical lines
are shown to facilitate comparison of the kinetic traces in
top
and
bottom
panel
. Reprinted from [
73
](
left
)and[
69
](
right
) with permission by Elsevier and by Copyright
2008 National Academy of Sciences, U.S.A., respectively
peptides and the membrane, fibril disaggregation into soluble backward oligomers
has been observed. [
74
] The disaggregation process is driven by entropy and results
in soluble protofibrillar oligomers. The protofibrillar oligomers are larger, more
ordered, and more stable than those observed during the aggregation process and,
importantly, are not detected in disaggregation simulations carried out in bulk
solution, i.e., in the absence of lipid vesicles.
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