As research progresses towards understanding the role of the amyloid-β (Aβ) in Alzheimer’s disease, certain aspects of the aggregation process for Aβ are still not clear. In particular, the accepted constitution of toxic aggregates in neurons has shifted towards small oligomers. However, the process of forming these oligomers in cells is still not fully clear. Even more interestingly, it has been implied that cell membranes, and, in particular, anionic lipids within those membranes, play a key role in the progression of Aβ aggregation, but the exact nature of the Aβ-membrane interaction in this process is still unknown. In this work, we use a thermodynamic cycle and umbrella sampling molecular dynamics to investigate dimerization of the 42-residue Aβ peptide on model zwitterionic dipalmitoylphosphatidylcholine (DPPC) or model anionic dioleoylphosphatidylserine (DOPS) bilayer surfaces. We determined that Aβ dimerization was strongly favored through interactions with the DOPS bilayer. Further, our calculations showed that the DOPS bilayer promoted strong protein-protein interactions within the Aβ dimer, while DPPC favored strong protein-lipid interactions. By promoting dimer formation and subsequent dimer release into the solvent, the DOPS bilayer acts as a catalyst in Aβ aggregation through converting Aβ monomers in solution into Aβ dimers in solution without substantial a free energy cost
