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Modulation of electrostatic interactions to reveal a reaction network unifying the aggregation behaviour of the Aβ42 peptide and its variants

Meisl, Georg; Yang, Xiaoting LU ; Dobson, Christopher M; Linse, Sara LU and Knowles, Tuomas P J (2017) In Chemical Science 8(6). p.4352-4362
Abstract

The aggregation of the amyloid β peptide (Aβ42), which is linked to Alzheimer's disease, can be altered significantly by modulations of the peptide's intermolecular electrostatic interactions. Variations in sequence and solution conditions have been found to lead to highly variable aggregation behaviour. Here we modulate systematically the electrostatic interactions governing the aggregation kinetics by varying the ionic strength of the solution. We find that changes in the solution ionic strength induce a switch in the reaction pathway, altering the dominant mechanisms of aggregate multiplication. This strategy thereby allows us to continuously sample a large space of different reaction mechanisms and develop a minimal reaction network... (More)

The aggregation of the amyloid β peptide (Aβ42), which is linked to Alzheimer's disease, can be altered significantly by modulations of the peptide's intermolecular electrostatic interactions. Variations in sequence and solution conditions have been found to lead to highly variable aggregation behaviour. Here we modulate systematically the electrostatic interactions governing the aggregation kinetics by varying the ionic strength of the solution. We find that changes in the solution ionic strength induce a switch in the reaction pathway, altering the dominant mechanisms of aggregate multiplication. This strategy thereby allows us to continuously sample a large space of different reaction mechanisms and develop a minimal reaction network that unifies the experimental kinetics under a wide range of different conditions. More generally, this universal reaction network connects previously separate systems, such as charge mutants of the Aβ42 peptide, on a continuous mechanistic landscape, providing a unified picture of the aggregation mechanism of Aβ42.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Chemical Science
volume
8
issue
6
pages
11 pages
publisher
Royal Society of Chemistry
external identifiers
  • scopus:85021747564
  • wos:000402384900023
ISSN
2041-6520
DOI
10.1039/c7sc00215g
language
English
LU publication?
yes
id
2fde8f1a-7311-4b52-b06c-fb3e5db0e280
date added to LUP
2017-07-20 06:53:51
date last changed
2017-09-18 11:38:46
@article{2fde8f1a-7311-4b52-b06c-fb3e5db0e280,
  abstract     = {<p>The aggregation of the amyloid β peptide (Aβ42), which is linked to Alzheimer's disease, can be altered significantly by modulations of the peptide's intermolecular electrostatic interactions. Variations in sequence and solution conditions have been found to lead to highly variable aggregation behaviour. Here we modulate systematically the electrostatic interactions governing the aggregation kinetics by varying the ionic strength of the solution. We find that changes in the solution ionic strength induce a switch in the reaction pathway, altering the dominant mechanisms of aggregate multiplication. This strategy thereby allows us to continuously sample a large space of different reaction mechanisms and develop a minimal reaction network that unifies the experimental kinetics under a wide range of different conditions. More generally, this universal reaction network connects previously separate systems, such as charge mutants of the Aβ42 peptide, on a continuous mechanistic landscape, providing a unified picture of the aggregation mechanism of Aβ42.</p>},
  author       = {Meisl, Georg and Yang, Xiaoting and Dobson, Christopher M and Linse, Sara and Knowles, Tuomas P J},
  issn         = {2041-6520},
  language     = {eng},
  number       = {6},
  pages        = {4352--4362},
  publisher    = {Royal Society of Chemistry},
  series       = {Chemical Science},
  title        = {Modulation of electrostatic interactions to reveal a reaction network unifying the aggregation behaviour of the Aβ42 peptide and its variants},
  url          = {http://dx.doi.org/10.1039/c7sc00215g},
  volume       = {8},
  year         = {2017},
}