Computational Model to Unravel the Function of Amyloid‑β Peptides in Contact with a Phospholipid Membrane

Divalent
cations have a strong impact on the properties of phospholipid
membranes, where amyloid-β peptides exert effects related to
possible functional or pathological roles. In this work, we use an
atomistic computational model of dimyristoyl-phosphatidylcholine (DMPC)
membrane bilayers. We perturb this model with a simple model of divalent cations (Mg2+) and with a single amyloid-β (Aβ) peptide of
42 residues, both with and without a single Cu2+ ion bound
to the N-terminus. In agreement with the 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 Aβ 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 the diluted Aβ peptide floating
around phospholipid membranes.