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Soluble Protofibrils as Metastable Intermediates in Simulations of Amyloid Fibril Degradation Induced by Lipid Vesicles


Friedman, R; Pellarin, R; Caflisch, A (2010). Soluble Protofibrils as Metastable Intermediates in Simulations of Amyloid Fibril Degradation Induced by Lipid Vesicles. Journal of Physical Chemistry Letters:471-474.

Abstract

Amyloid fibril disaggregation has been observed recently upon
incubation with lipid vesicles, challenging the view of fibrils as end states of the
aggregation process in vivo. Here, we follow fibril disaggregation in the presence
of lipid vesicles by means of molecular dynamics simulations, using simplified
models of peptides and lipids. The simulation results show that disaggregation is
driven by an entropy increase and yields soluble protofibrillar intermediates.
These intermediates are different fromthemetastable oligomers observed during
fibril formation, and their stability depends on the morphology of the parent
fibril.

Abstract

Amyloid fibril disaggregation has been observed recently upon
incubation with lipid vesicles, challenging the view of fibrils as end states of the
aggregation process in vivo. Here, we follow fibril disaggregation in the presence
of lipid vesicles by means of molecular dynamics simulations, using simplified
models of peptides and lipids. The simulation results show that disaggregation is
driven by an entropy increase and yields soluble protofibrillar intermediates.
These intermediates are different fromthemetastable oligomers observed during
fibril formation, and their stability depends on the morphology of the parent
fibril.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Department of Biochemistry
07 Faculty of Science > Department of Biochemistry
Dewey Decimal Classification:570 Life sciences; biology
Date:2010
Deposited On:10 Mar 2010 06:36
Last Modified:17 Feb 2018 16:58
Publisher:American Chemical Society
ISSN:1948-7185
OA Status:Closed
Free access at:Related URL. An embargo period may apply.
Publisher DOI:https://doi.org/10.1021/jz900318t
Related URLs:http://www.biochem-caflisch.uzh.ch/static/pdf/ran10_jcpl.pdf

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