Nucleation of protein fibrillation by nanoparticles
- 22 May 2007
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 104 (21), 8691-8696
- https://doi.org/10.1073/pnas.0701250104
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.Keywords
This publication has 58 references indexed in Scilit:
- Understanding the nanoparticle–protein corona using methods to quantify exchange rates and affinities of proteins for nanoparticlesProceedings of the National Academy of Sciences of the United States of America, 2007
- Novel Method to Prepare Morphologically Rich Polymeric Surfaces for Biomedical Applications via Phase Separation and Arrest of Microgel ParticlesThe Journal of Physical Chemistry B, 2006
- The Kinetics of Nucleated Polymerizations at High Concentrations: Amyloid Fibril Formation Near and Above the “Supercritical Concentration”Biophysical Journal, 2006
- Fluorescent Nanocrystals as Colloidal Probes in Complex Fluids Measured by Fluorescence Correlation SpectroscopySmall, 2005
- Dynamics in the Unfolded State of β2-microglobulin Studied by NMRJournal of Molecular Biology, 2005
- Natural oligomers of the amyloid-β protein specifically disrupt cognitive functionNature Neuroscience, 2004
- Phospholipid Catalysis of Diabetic Amyloid AssemblyJournal of Molecular Biology, 2004
- Hierarchical Assembly of β2-Microglobulin Amyloid In Vitro Revealed by Atomic Force MicroscopyJournal of Molecular Biology, 2003
- MOLMOL: A program for display and analysis of macromolecular structuresJournal of Molecular Graphics, 1996
- A new form of amyloid protein associated with chronic hemodialysis was identified as β2-microglobulinBiochemical and Biophysical Research Communications, 1985