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Nucleation of protein fibrillation by nanoparticles (in PNAS vol. 104 no. 21)
Bibliografi
Author:
Linse, Sara
;
Cabaleiro-Lago, Celia
;
Xue, Wei-Feng
;
Lynch, Iseult
;
Lindman, Stina
;
Thulin, Eva
;
Radford, Sheena E.
;
Dawson, Kenneth A.
Topik:
Amyloid
;
Nanotoxicology
;
Surface-Assisted Nucleation
;
Nanotechnology
Bahasa:
(EN )
Edisi:
May 2007
Penerbit:
National Academy of Sciences
Tempat Terbit:
Washington, D.C.
Tahun Terbit:
2007
Penyerta:
http://www.pnas.org/content/suppl/2007/04/25/07012
Jenis:
Article - diterbitkan di jurnal ilmiah internasional
Fulltext:
8691.full.pdf
(1.09MB;
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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 m-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 m-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.
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