Nucleation of protein fibrillation by nanoparticles.

Linse, Sara, Cabaleiro-Lago, Celia, Xue, Wei-Feng, Lynch, Iseult, Lindman, Stina, Thulin, Eva, Radford, Sheena E., Dawson, Kenneth A (2007) Nucleation of protein fibrillation by nanoparticles. Proceedings of the National Academy of Sciences of the United States of America, 104 (21). pp. 8691-8696. ISSN 0027-8424. (doi:10.1073/pnas.0701250104)

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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 surface-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.

Item Type: Article
DOI/Identification number: 10.1073/pnas.0701250104
Subjects: Q Science > QC Physics
Q Science > QD Chemistry
Q Science > QP Physiology (Living systems) > QP517 Biochemistry
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: Wei-Feng Xue
Date Deposited: 11 Jun 2013 13:11 UTC
Last Modified: 29 May 2019 10:17 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/34253 (The current URI for this page, for reference purposes)
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