Hydrodynamic Effects on Amyloid-β Aggregation

Abstract

The self-assembly of misfolded amyloid-β (Aβ) proteins into insoluble fibrils is strongly linked to the pathogenesis of Alzheimer's disease (AD). The development of new drugs capable to inhibit fibril formation requires the understanding of the mechanism leading to the formation, in the early stages, of metastable oligomers which are the main neurotoxic species.Our investigation enlighten the role of hydrodynamic interactions (HI) in the kinetics of β-amyloidogenesis, interactions which are essential for modelling such processes occurring in highly crowed environments like cells [1].Our approach is based on a new multi-scale and multi-physics method that couples Lattice Boltzmann and Molecular Dynamics (LBMD) techniques[2,3]. In our scheme solvent mediated interactions are included naturally. For the molecular system we adopt the high resolution coarse-grained model OPEP (Optimized Potential for Efficient Protein structure prediction)[4], developed in our laboratory. For the first time, we have performed quasi all-atoms simulations for very large systems containing thousands of amyloid peptides and approaching experimental concentration. After the correct tuning of the key parameter of our coupling in order to obtain the experimental diffusivity of Aβ monomer and small oligomers, we have demonstrated that HI speed up the aggregation process. In our poster we will present a detailed characterisation of the fluctuating clusters in term of their size and the structural organisation of the peptides.