Effects of graphitic nanomaterials on the dissociation pathway of amyloidogenic peptide dimer

The potential for nanomaterials to interact with biological molecules has been under significant scrutiny, specifically, in their possible role as scaffolds for protein aggregation that can result in various amyloid diseases. Here, we employed classical molecular dynamics simulations to investigate the effects of graphitic carbon nanomaterials on the structure, dynamics and dissociation pathway of a previously identified preformed dimer of amyloidogenic apoC-II(60-70) peptide [1, 2]. Our results showed the dimer interacting with the graphitic nanoparticles through π-π interactions. Free energy of dissociation calculations showed that the dimer is weakly bound to the C60 nanoparticle, while it is more strongly interacting with the elongated nanomaterials, such as carbon nanotube and graphene. The significant curvature of the C60 surface induced an increase in peptide mobility, which contributed to the weaker binding and dissociation of the dimer from the C60 surface. This suggests that C60 can act as a potential inhibitor for fibril growth. On the other hand, the stronger interactions between the elongated carbon nanomaterials and the apoC-II(60-70) dimer resulted in a separation of the dimer with one strand remaining adsorbed on the surface of the nanomaterial during the in-silico pull-off experiment. This suggests that the interaction between the bound peptide and the flat graphitic surfaces is stronger than the interactions between the peptide strands themselves. Our results suggest that flat surface carbon nanomaterials present favorable binding substrates for aromatic-rich peptides, and thus have the ability to act as templates to mediate peptide self-assembly and fibril growth.