Changing the amyloid nucleation process using small molecules and substrates: a way to build two-dimensional...

The assembly of two-dimensional (2D) materials on substrates presents a wide range of potential applications in nanomaterials. However, there is limited information available in the literature regarding the tunable nucleation process in molecular assembly. In this paper, a neurodegenerative disease-related short peptide and a small molecule named Fast Green (FG) were selected for their binding affinity with mica/highly oriented pyrolytic graphite (HOPG) substrates. Based on atomic force microscopy (AFM) and molecular dynamics (MD) simulation, we investigated the control of 2D assemblies. By tuning FG small molecules and substrates, the assemblies grew epitaxially from nanosheets to nanofilms on mica and highly ordered nanofilaments on HOPG substrates. Notably, the nuclei formed an orderly array without a critical size or lag phase in the presence of FG molecules on the HOPG substrate, facilitating a quicker co-assembly of ordered filaments compared to bulk conditions. Our MD simulations further demonstrated that the interaction between Aβ_16-22 molecules and the HOPG substrate was primarily due to π-π interactions between aromatic rings, which led to the formation of single-layer filaments by lying on the surface of HOPG. Additionally, parallel π-π stacking acted as the primary force to inhibit the aggregation of peptides into fibrils. Overall, our results provide a strategy for modulating the interaction of amyloid peptides with small molecules and substrates in the assembly of 2D nanomaterials.