Comparative Molecular Dynamics Study of Aβ Adsorption on the Self-Assembled Monolayers

The adsorption and aggregation of the amyloid-beta (Abeta) peptides on the cell membrane plays a causal role in the pathogenesis of Alzheimer's disease. Here, we report all-atom molecular dynamics (MD) simulations to study the interactions of Abeta oligomer with self-assembled monolayers (SAMs) terminated with hydrophobic CH(3) and hydrophilic OH functional groups, with particular interests in how surface chemistry and Abeta orientation affect the adsorption behavior of Abeta. Simulation results show that the CH(3)-SAM has a stronger binding affinity to Abeta than the OH-SAM does, although both surfaces can induce Abeta adsorption. Regardless of the characteristics of the surface, the hydrophobic C-terminal region is more likely to be adsorbed on the SAMs, indicating a preferential orientation and interface for Abeta adsorption. Structural and energetic comparison among six Abeta-SAM systems further reveals that Abeta orientation, SAM surface hydrophobicity, and interfacial waters all determine Abeta adsorption behavior on the surface, highlighting the importance of hydrophobic interactions at the interface. This work may provide parallel insights into the interactions of Abeta with lipid bilayers.