Inhibition of amyloid β protein fibrillation by polymeric nanoparticles

Copolymeric NiPAM:BAM nanoparticles of varying hydrophobicity were found to retard fibrillation of the Alzheimer's disease-associated amyloid β protein (Aβ). We found that these nanoparticles affect mainly the nucleation step of Aβ fibrillation. The elongation step is largely unaffected by the particles, and once the Aβ 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 Aβ is strongly dependent on both the amount and surface character of the nanoparticles. Surface plasmon resonance studies show that Aβ 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 Aβ and prefibrillar oligomers to the nanoparticles prevents fibrillation. Moreover, we find that fibrillation of Aβ initiated in the absence of nanoparticles can be reversed by addition of nanoparticles up to a particular time point before mature fibrils appear.