Membrane surfaces can accelerate amyloid $beta$ (A$beta$) aggregation, yet the role of membrane curvature in this process remains poorly understood. Here, we used multi-million atom all-atom molecular dynamics simulations to compare the adsorption, conformational dynamics, and oligomerization of four A$beta$42 peptides at a planar neuronal membrane and a highly curved lipid vesicle. For both systems, all peptides adsorbed within the first 2 $mu$s, but their subsequent behavior differed substantially. The curved membrane exhibited a larger area per lipid and more extensive hydrophobic packing defects, allowing A$beta$42 to penetrate more deeply and form strong contacts with lipid tails through its central hydrophobic core and C-terminal region. These interactions disrupted a solution-formed dimer and limited peptide-peptide association during the simulated interval. Additionally, vesicle-bound peptides adopted more extended conformations with increased $beta$-structure and $beta$-hairpin formation compared with peptides at the planar membrane. A$beta$42 adsorption was also corelated to lipid reorganization in the vesicle. In contrast, the planar membrane supported weaker adsorption and stable dimer-to-trimer growth but showed little large-scale lipid segregation. These findings reveal that curvature reshapes the early A$beta$42 aggregation landscape by strengthening peptide-lipid interactions, altering aggregation-prone conformations, and reorganizing membrane domains. Membrane geometry should therefore be considered alongside lipid composition in mechanistic models of A$beta$42 oligomerization and membrane-associated toxicity.
Maximiano, P., Hashemi, M.
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