Nucleation of protein fibrillation by nanoparticles
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/651288
- author
- Linse, Sara LU ; Cabaleiro-Lago, Celia ; Xue, Wei-Feng ; Lynch, Iseult ; Lindman, Stina LU ; Thulin, Eva LU ; Radford, Sheena E. and Dawson, Kenneth A.
- organization
- publishing date
- 2007
- 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 Academy of 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
- 2016-04-01 12:26:00
- date last changed
- 2022-04-21 07:10:41
@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}},
keywords = {{surface-assisted nucleation; amyloid; nanotoxicology}},
language = {{eng}},
number = {{21}},
pages = {{8691--8696}},
publisher = {{National Academy of 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}},
doi = {{10.1073/pnas.0701250104}},
volume = {{104}},
year = {{2007}},
}