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Nucleation of protein fibrillation by nanoparticles

Linse, Sara LU ; Cabaleiro-Lago, Celia; Xue, Wei-Feng; Lynch, Iseult; Lindman, Stina LU ; Thulin, Eva LU ; Radford, Sheena E. and Dawson, Kenneth A. (2007) In Proceedings of the National Academy of Sciences 104(21). p.8691-8696
Abstract
Nanoparticles present enormous surface areas and are found to enhance the rate of protein fibrillation by decreasing the lag time for nucleation. Protein fibrillation is involved in many human diseases, including Alzheimer's, Creutzfeld-Jacob disease, and dialysis-related amyloidosis. Fibril formation occurs by nucleation-dependent kinetics, wherein formation of a critical nucleus is the key rate-determining step, after which fibrillation proceeds rapidly. We show that nanoparticles (copolymer particles, cerium oxide particles, quantum dots, and carbon nanotubes) enhance the probability of appearance of a critical nucleus for nucleation of protein fibrils from human beta(2)-microglobulin. The observed shorter lag (nucleation) phase depends... (More)
Nanoparticles present enormous surface areas and are found to enhance the rate of protein fibrillation by decreasing the lag time for nucleation. Protein fibrillation is involved in many human diseases, including Alzheimer's, Creutzfeld-Jacob disease, and dialysis-related amyloidosis. Fibril formation occurs by nucleation-dependent kinetics, wherein formation of a critical nucleus is the key rate-determining step, after which fibrillation proceeds rapidly. We show that nanoparticles (copolymer particles, cerium oxide particles, quantum dots, and carbon nanotubes) enhance the probability of appearance of a critical nucleus for nucleation of protein fibrils from human beta(2)-microglobulin. The observed shorter lag (nucleation) phase depends on the amount and nature of particle surface. There is an exchange of protein between solution and nanoparticle surface, and beta(2)-Microglobulin forms multiple layers on the particle surface, providing a locally increased protein concentration promoting oligomer formation. This and the shortened lag phase suggest a mechanism involving surf ace-assisted nucleation that may increase the risk for toxic cluster and amyloid formation. It also opens the door to new routes for the controlled self-assembly of proteins and peptides into novel nanomaterials. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
surface-assisted nucleation, amyloid, nanotoxicology
in
Proceedings of the National Academy of Sciences
volume
104
issue
21
pages
8691 - 8696
publisher
National Acad Sciences
external identifiers
  • wos:000246853700005
  • scopus:34547454920
ISSN
1091-6490
DOI
10.1073/pnas.0701250104
language
English
LU publication?
yes
id
a87f726c-1d69-43f7-a1ce-16873c568383 (old id 651288)
date added to LUP
2007-12-13 08:12:42
date last changed
2017-11-05 03:45:43
@article{a87f726c-1d69-43f7-a1ce-16873c568383,
  abstract     = {Nanoparticles present enormous surface areas and are found to enhance the rate of protein fibrillation by decreasing the lag time for nucleation. Protein fibrillation is involved in many human diseases, including Alzheimer's, Creutzfeld-Jacob disease, and dialysis-related amyloidosis. Fibril formation occurs by nucleation-dependent kinetics, wherein formation of a critical nucleus is the key rate-determining step, after which fibrillation proceeds rapidly. We show that nanoparticles (copolymer particles, cerium oxide particles, quantum dots, and carbon nanotubes) enhance the probability of appearance of a critical nucleus for nucleation of protein fibrils from human beta(2)-microglobulin. The observed shorter lag (nucleation) phase depends on the amount and nature of particle surface. There is an exchange of protein between solution and nanoparticle surface, and beta(2)-Microglobulin forms multiple layers on the particle surface, providing a locally increased protein concentration promoting oligomer formation. This and the shortened lag phase suggest a mechanism involving surf ace-assisted nucleation that may increase the risk for toxic cluster and amyloid formation. It also opens the door to new routes for the controlled self-assembly of proteins and peptides into novel nanomaterials.},
  author       = {Linse, Sara and Cabaleiro-Lago, Celia and Xue, Wei-Feng and Lynch, Iseult and Lindman, Stina and Thulin, Eva and Radford, Sheena E. and Dawson, Kenneth A.},
  issn         = {1091-6490},
  keyword      = {surface-assisted nucleation,amyloid,nanotoxicology},
  language     = {eng},
  number       = {21},
  pages        = {8691--8696},
  publisher    = {National Acad Sciences},
  series       = {Proceedings of the National Academy of Sciences},
  title        = {Nucleation of protein fibrillation by nanoparticles},
  url          = {http://dx.doi.org/10.1073/pnas.0701250104},
  volume       = {104},
  year         = {2007},
}