Nucleation of protein fibrillation by nanoparticles

Linse, SaraLund University,Lunds universitet,Biofysikalisk kemi,Centrum för Molekylär Proteinvetenskap,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Biophysical Chemistry,Center for Molecular Protein Science,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH (author)

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.

Cabaleiro-Lago, Celia (author)
Xue, Wei-Feng (author)
Lynch, Iseult (author)
Lindman, StinaLund University,Lunds universitet,Biofysikalisk kemi,Centrum för Molekylär Proteinvetenskap,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Biophysical Chemistry,Center for Molecular Protein Science,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH(Swepub:lu)bpc-sli (author)
Thulin, EvaLund University,Lunds universitet,Biofysikalisk kemi,Centrum för Molekylär Proteinvetenskap,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Biophysical Chemistry,Center for Molecular Protein Science,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH(Swepub:lu)fkm2-eth (author)
Radford, Sheena E. (author)
Dawson, Kenneth A. (author)
Biofysikalisk kemiCentrum för Molekylär Proteinvetenskap (creator_code:org_t)

In:Proceedings of the National Academy of Sciences: Proceedings of the National Academy of Sciences104:21, s. 8691-86961091-64900027-8424

By the author/editor: Linse, Sara; Cabaleiro-Lago, ...; Xue, Wei-Feng; Lynch, Iseult; Lindman, Stina; Thulin, Eva; show more...; Radford, Sheena ...; Dawson, Kenneth ...; show less...

About the subject

NATURAL SCIENCES: NATURAL SCIENCES; and Chemical Science ...; and Physical Chemist ...

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