Journal
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume 130, Issue 46, Pages 15437-15443Publisher
AMER CHEMICAL SOC
DOI: 10.1021/ja8041806
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Funding
- EU FP6 NanoInteract
- EU MC RTN CIPSNAC
- EPA Ireland
- IRCSET
- Ministerio de Educacion y Ciencia
- Swedish Research Council
- SFI Walton
- Welcome Trust [067660]
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Copolymeric NiPAM:BAM nanoparticles of varying hydrophobicity were found to retard fibrillation of the Alzheimer's disease-associated amyloid beta protein (A beta). We found that these nanoparticles affect mainly the nucleation step of A beta fibrillation. The elongation step is largely unaffected by the particles, and once the M is nucleated, the fibrillation process occurs with the same rate as in the absence of nanoparticles. The extension of the lag phase for fibrillation of A beta is strongly dependent on both the amount and surface character of the nanoparticles. Surface plasmon resonance studies show that A beta binds to the nanoparticles and provide rate and equilibrium constants for the interaction. Numerical analysis of the kinetic data for fibrillation suggests that binding of monomeric A beta and prefibrillar oligomers to the nanoparticles prevents fibrillation. Moreover, we find that fibrillation of A beta initiated in the absence of nanoparticles can be reversed by addition of nanoparticles up to a particular time point before mature fibrils appear.
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