title: Size distribution of amyloid nanofibrils.
abstract: We consider the size distribution of amyloid nanofibrils (protofilaments) in nucleating protein solutions when the nucleation process occurs by the mechanism of direct polymerization of β-strands (extended peptides or protein segments) into β-sheets. Employing the atomistic nucleation theory, we derive a general expression for the stationary size distribution of amyloid nanofibrils constituted of successively layered β-sheets. The application of this expression to amyloid β(1-40) (Aβ(40)) fibrils allows us to determine the nanofibril size distribution as a function of the protein concentration and temperature. The distribution is most remarkable with its exhibiting a series of peaks positioned at "magic" nanofibril sizes (or lengths), which are due to deep local minima in the work for fibril formation. This finding of magic sizes or lengths is consistent with experimental results for the size distribution of aggregates in solutions of Aβ(40) proteins. Also, our approach makes it possible to gain insight into the effect of point mutations on the nanofibril size distribution, an effect that may play a role in experimentally observed substantial differences in the fibrillation lag-time of wild-type and point-mutated amyloid-β proteins.
authors: Centre for Molecular Nanoscience, School of Chemistry, University of Leeds, Leeds, United Kingdom.
authors: Raffaela
authors: R
authors: Cabriolu
authors: Dimo
authors: D
authors: Kashchiev
authors: Stefan
authors: S
authors: Auer
mesh_terms: D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry*; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000235:genetics; D057139:Nanofibers / Q000737:chemistry*; D010316:Particle Size; D017354:Point Mutation / Q000235:genetics; D017433:Protein Structure, Secondary; D012995:Solubility; D013816:Thermodynamics
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides