Interaction of A β 1 − 42 chains and fibrillary seeds studied by all-atom molecular dynamics simulations

We apply all-atom molecular dynamics simulations to investigate interactions of amyloid beta (A$\beta$) fibril seeds with natively disordered A$\beta$ chains, a process associated with the onset of Alzheimer's disease. The simulations captured attachment of A$\beta$ chains to the fibrils suggesting an onset of both fibril's elongation and secondary nucleation, with a stronger affinity of attachment leading to elongation. Choice of fibril's model appears important for the propensity to recruit A$\beta$ chains from solution and retain them adsorbed. Nuclear magnetic resonance-based and cryo-electron microscopy derived models of A$\beta$ fibrils exhibited significant differences in the interaction with individual A$\beta$ chains, as well as in structural and dynamical stability in solution.