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Surface Effects on Aggregation Kinetics of Amyloidogenic Peptides

Vacha, Robert; Linse, Sara LU and Lund, Mikael LU (2014) In Journal of the American Chemical Society 136(33). p.11776-11782
Abstract
The presence of surfaces influences the fibril formation kinetics of peptides and proteins. We present a systematic study of the aggregation kinetics of amyloidogenic peptides caused by different surfaces using molecular simulations of model peptides and thioflavin T fluorescence experiments. Increasing the monomer surface attraction affects the nucleation and growth of small oligomers in a nonlinear manner: Weakly attractive surfaces lead to retardation; strongly attractive surfaces lead to acceleration. Further, the same type of surface either accelerates or retards growth, depending on the bulk propensity of the peptide to form fibrils: An attractive surface retards fibril formation of peptides with a high tendency for fibril formation,... (More)
The presence of surfaces influences the fibril formation kinetics of peptides and proteins. We present a systematic study of the aggregation kinetics of amyloidogenic peptides caused by different surfaces using molecular simulations of model peptides and thioflavin T fluorescence experiments. Increasing the monomer surface attraction affects the nucleation and growth of small oligomers in a nonlinear manner: Weakly attractive surfaces lead to retardation; strongly attractive surfaces lead to acceleration. Further, the same type of surface either accelerates or retards growth, depending on the bulk propensity of the peptide to form fibrils: An attractive surface retards fibril formation of peptides with a high tendency for fibril formation, while the same surface accelerates fibril formation of peptides with a low propensity for fibril formation. The surface effect is thus determined by the relative association propensity of peptides for the surface compared to bulk and by the surface area to protein concentration ratio. This rationalization is in agreement with the measured fibrillar growth of a-synuclein from Parkinson and amyloid beta peptide from Alzheimer disease in the presence of surface area introduced in a controlled way in the form of nanoparticles. These findings offer molecular insight into amyloid formation kinetics in complex environments and may be used to tune fibrillation properties in diverse systems. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of the American Chemical Society
volume
136
issue
33
pages
11776 - 11782
publisher
The American Chemical Society
external identifiers
  • wos:000340737900033
  • scopus:84906330021
ISSN
1520-5126
DOI
10.1021/ja505502e
language
English
LU publication?
yes
id
c21b1ef3-9037-420d-8a30-30de59492dd3 (old id 4648977)
date added to LUP
2014-09-24 09:20:54
date last changed
2017-11-05 03:52:55
@article{c21b1ef3-9037-420d-8a30-30de59492dd3,
  abstract     = {The presence of surfaces influences the fibril formation kinetics of peptides and proteins. We present a systematic study of the aggregation kinetics of amyloidogenic peptides caused by different surfaces using molecular simulations of model peptides and thioflavin T fluorescence experiments. Increasing the monomer surface attraction affects the nucleation and growth of small oligomers in a nonlinear manner: Weakly attractive surfaces lead to retardation; strongly attractive surfaces lead to acceleration. Further, the same type of surface either accelerates or retards growth, depending on the bulk propensity of the peptide to form fibrils: An attractive surface retards fibril formation of peptides with a high tendency for fibril formation, while the same surface accelerates fibril formation of peptides with a low propensity for fibril formation. The surface effect is thus determined by the relative association propensity of peptides for the surface compared to bulk and by the surface area to protein concentration ratio. This rationalization is in agreement with the measured fibrillar growth of a-synuclein from Parkinson and amyloid beta peptide from Alzheimer disease in the presence of surface area introduced in a controlled way in the form of nanoparticles. These findings offer molecular insight into amyloid formation kinetics in complex environments and may be used to tune fibrillation properties in diverse systems.},
  author       = {Vacha, Robert and Linse, Sara and Lund, Mikael},
  issn         = {1520-5126},
  language     = {eng},
  number       = {33},
  pages        = {11776--11782},
  publisher    = {The American Chemical Society},
  series       = {Journal of the American Chemical Society},
  title        = {Surface Effects on Aggregation Kinetics of Amyloidogenic Peptides},
  url          = {http://dx.doi.org/10.1021/ja505502e},
  volume       = {136},
  year         = {2014},
}