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Retardation of Abeta fibril formation by phospholipid vesicles depends on membrane phase behavior.

Hellstrand, Erik LU ; Sparr, Emma LU and Linse, Sara LU (2010) In Biophysical Journal 98(10). p.2206-2214
Abstract
An increasing amount of evidence suggests that in several amyloid diseases, the fibril formation in vivo and the mechanism of toxicity both involve membrane interactions. We have studied Alzheimer's disease related amyloid beta peptide (Abeta). Recombinant Abeta(M1-40) and Abeta(M1-42) produced in Escherichia coli, allows us to carry out large scale kinetics assays with good statistics. The amyloid formation process is followed in means of thioflavin T fluorescence at relatively low (down to 380 nM) peptide concentration approaching the physiological range. The lipid membranes are introduced in the system as large and small unilamellar vesicles. The aggregation lagtime increases in the presence of lipid vesicles for all situations... (More)
An increasing amount of evidence suggests that in several amyloid diseases, the fibril formation in vivo and the mechanism of toxicity both involve membrane interactions. We have studied Alzheimer's disease related amyloid beta peptide (Abeta). Recombinant Abeta(M1-40) and Abeta(M1-42) produced in Escherichia coli, allows us to carry out large scale kinetics assays with good statistics. The amyloid formation process is followed in means of thioflavin T fluorescence at relatively low (down to 380 nM) peptide concentration approaching the physiological range. The lipid membranes are introduced in the system as large and small unilamellar vesicles. The aggregation lagtime increases in the presence of lipid vesicles for all situations investigated and the phase behavior of the membrane in the vesicles has a large effect on the aggregation kinetics. By comparing vesicles with different membrane phase behavior we see that the solid gel phase dipalmitoylphosphatidylcholine bilayers cause the largest retardation of Abeta fibril formation. The membrane-induced retardation reaches saturation and is present when the vesicles are added during the lag time up to the nucleation point. No significant difference is detected in lag time when increasing amount of negative charge is incorporated into the membrane. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Biophysical Journal
volume
98
issue
10
pages
2206 - 2214
publisher
Cell Press
external identifiers
  • pmid:20483329
  • wos:000277858400022
  • scopus:77952758210
ISSN
1542-0086
DOI
10.1016/j.bpj.2010.01.063
language
English
LU publication?
yes
id
4ec8f378-03f8-45db-a649-dcace4d220c5 (old id 1610120)
date added to LUP
2010-06-02 12:31:34
date last changed
2018-06-03 03:03:02
@article{4ec8f378-03f8-45db-a649-dcace4d220c5,
  abstract     = {An increasing amount of evidence suggests that in several amyloid diseases, the fibril formation in vivo and the mechanism of toxicity both involve membrane interactions. We have studied Alzheimer's disease related amyloid beta peptide (Abeta). Recombinant Abeta(M1-40) and Abeta(M1-42) produced in Escherichia coli, allows us to carry out large scale kinetics assays with good statistics. The amyloid formation process is followed in means of thioflavin T fluorescence at relatively low (down to 380 nM) peptide concentration approaching the physiological range. The lipid membranes are introduced in the system as large and small unilamellar vesicles. The aggregation lagtime increases in the presence of lipid vesicles for all situations investigated and the phase behavior of the membrane in the vesicles has a large effect on the aggregation kinetics. By comparing vesicles with different membrane phase behavior we see that the solid gel phase dipalmitoylphosphatidylcholine bilayers cause the largest retardation of Abeta fibril formation. The membrane-induced retardation reaches saturation and is present when the vesicles are added during the lag time up to the nucleation point. No significant difference is detected in lag time when increasing amount of negative charge is incorporated into the membrane.},
  author       = {Hellstrand, Erik and Sparr, Emma and Linse, Sara},
  issn         = {1542-0086},
  language     = {eng},
  number       = {10},
  pages        = {2206--2214},
  publisher    = {Cell Press},
  series       = {Biophysical Journal},
  title        = {Retardation of Abeta fibril formation by phospholipid vesicles depends on membrane phase behavior.},
  url          = {http://dx.doi.org/10.1016/j.bpj.2010.01.063},
  volume       = {98},
  year         = {2010},
}