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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4648977
- author
- Vacha, Robert
; Linse, Sara
LU
and Lund, Mikael
LU
- organization
- publishing date
- 2014
- 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 (ACS)
- external identifiers
-
- wos:000340737900033
- scopus:84906330021
- pmid:25068615
- ISSN
- 1520-5126
- DOI
- 10.1021/ja505502e
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Biochemistry and Structural Biology (S) (000006142), Theoretical Chemistry (S) (011001039)
- id
- c21b1ef3-9037-420d-8a30-30de59492dd3 (old id 4648977)
- date added to LUP
- 2016-04-01 13:06:14
- date last changed
- 2023-04-06 00:09:44
@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 (ACS)}},
series = {{Journal of the American Chemical Society}},
title = {{Surface Effects on Aggregation Kinetics of Amyloidogenic Peptides}},
url = {{http://dx.doi.org/10.1021/ja505502e}},
doi = {{10.1021/ja505502e}},
volume = {{136}},
year = {{2014}},
}