Journal of the American Chemical Society, Vol.130, No.46, 15437-15443, 2008
Inhibition of Amyloid beta Protein Fibrillation by Polymeric Nanoparticles
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.