A computational model to unravel the function of amyloid-βpeptide in contact with a phospholipid membrane

The normal synapse activity involves the release of copper and other divalent cations in the synaptic region. These ions have a strong impact on the membrane properties, especially when the membrane has charged groups, like it is the case of synapse. In this work we use an atomistic computational model of dimyristoyl-phosphatidylcholine (DMPC) membrane bilayer. We perturb this model with a simple model of divalent cation (Mg 2+ ), and with a single amyloid- β (A β ) peptide of 42 residues, both with and without a single Cu 2+ ion bound to the N-terminus. In agreement with experimental results reported in the literature, the model confirms that divalent cations locally destabilize the DMPC membrane bilayer, and, for the first time, that the monomeric form of A β helps in avoiding the interactions between divalent cations and DMPC, preventing significant effects on the DMPC bilayer properties. These results are discussed in the frame of a protective role of diluted A β peptide floating in the synaptic region. Author summary We modelled the behavior of a Mg 2+ divalent cation, with the size of Zn 2+ and Cu 2+ , in contact with a phosphatidyl lipid bilayer. We also modelled the monomeric amyloid- β peptide 1-42, both free and Cu-loaded, the latter mimicking the final step of the binding between the peptide and the divalent cation. On the basis of the simulation results, we propose that the peptide hinders the strong interactions between the divalent cation and the membrane.