Nucleation of protein fibrillation by nanoparticles

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 104; no. 21; pp. 8691 - 8696
• Main Authors: Linse, Sara, Cabaleiro-Lago, Celia, Xue, Wei-Feng, Lynch, Iseult, Lindman, Stina, Thulin, Eva, Radford, Sheena E, Dawson, Kenneth A
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 22-05-2007; National Acad Sciences
• Series: From the Cover
• Subjects: amyloid; Amyloids; beta 2-Microglobulin - chemistry; beta 2-Microglobulin - ultrastructure; Biochemistry; Biological Sciences; Calorimetry; Chemical Sciences; Copolymers; Fibrillation; Fluorescence; Fysikalisk kemi; Humans; Kemi; Kinetics; Models, Molecular; Nanoparticles; Nanoparticles - chemistry; Nanoparticles - ultrastructure; nanotoxicology; Natural Sciences; Naturvetenskap; Nucleation; Pathology; Phosphates; Physical Chemistry; Physical Sciences; Protein Structure, Tertiary; Proteins; Self assembly; Sodium; Solar fibrils; surface-assisted nucleation; Toxicology
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.0701250104

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 β₂-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 β₂-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.