Study On The Interactions Between Graphene/Graphene Oxide And Biomolecules

Because of their excellent physical and chemical properties, pristine graphene (PG) and its derivative graphene oxide (GO) have exhibited growing potential in various biomedical applications, such as drug delivery and biosensors, and have spurred an increasing interest in recent years. PG is a one-atom-thick sheet of carbon atoms arrayed in a honeycomb pattern. GO is a versatile derivative of PG, with carboxylic groups at its edges, hydroxyl and epoxy groups on its basal plane, and carbon-carbon sp2 hydrophobic domains. In biological experiments, one has to adopt GO instead of PG to achieve better water-solubility. However, there exist various experimental phenomena of interactions between GO and biomolecules. Since the molecular structure of GO is amorphous and nonstoichiometric, the molecular mechanism remains unclear.Molecular dynamics (MD) simulation can provide detailed information about the interactions between biomolecules and carbon-based nanoparticles that complements experiments. Therefore, MD simulation is an effective auxiliary method of experimental research, which is of great importance to understand the bioeffects of carbon nanoparticles, such as PG or GO. In this dissertation, we will employ MD simulations to investigate the interactions between PG/GO and biomolecules, namely, peptides, proteins, DNA segments and lipid bilayers.At first, we have studied the adsorption and aggregation of peptide Vprl3-33 onto PG and uniformly and randomly oxidized GO. The results showed that Vpr 13-33 was adsorbed on the surface of PG and GO and lost its secondary and tertiary structures, but GO had weaker effect on the structure of Vpr13-33 compared with PG. We then continued to simulate the adsorption of protein GA module (GA53) onto GO, compared with similar adsorption on PG. We found that:(1) the protein GA53 can be easily and firmly adsorbed onto the surface of GO and PG, but the binding sites are not specific; the main difference is that the secondary structure of GA53 can be well preserved in protein-GO system, while GA53 will partially lose its secondary structure after adsorbed on PG. (2) in protein-GO system, hydroxyl and epoxy groups increase the distance between protein and GO, which weaken their vdW interactions, meanwhile, hydrogen bonds and electrostatic interactions enhance their binding affinity. In protein-PG system, strong vdW interactions between residues of GA53 and PG have destroyed its secondary structure. (3) n-n stacking interactions still exist between aromatic residues and both the basal plane of GO and PG. In comparison with PG, our results suggest that uniformly and randomly oxidized GO presents better biocompatibility to preserve protein secondary structure when simultaneously absorbing protein.Then, we continued to perform MD simulations to explore the dynamic process of both single-stranded (ss) and double-stranded (ds) DNA segments adsorption on PG/GO in aqueous solution. The results showed that the ssDNA was firmly adsorbed and lay flat on the surface of PG and GO, but dsDNA could not lie flat but stood upright on their surfaces, which were well consistent with experimental speculations. With the longer basepairs, strong electrostatic repulsion makes the DNA segment cannot stay with its axis parallel to the basal plane of GO but rotate rapidly till vertically located on the surface of GO. Exploration on the mechanism of DNA segments binding to PG and GO indicates that π-π stacking interaction is the dominant force in the adsorption of DNA segments on PG, while both π-π stacking and hydrogen bonding contribute to the binding affinity between DNA segments and GO. It was clear that oxygen-contained groups on GO surface enrich the interactions between GO and biomolecules, and GO possesses strong adsorption capacity. Our simulations confirmed that the fundamental principle of biosensors based on GO is GO’s preferential adsorption with ssDNA over dsDNA.Finally, we simulated the spontaneous penetration of PG into membrane and the orientation of PG therein. Our results showed that PG could readily move into the DPPC bilayer and stay there with its plane not vertical but parallel to the lipid tails, which was different from other simulations by coarse-grained model. Things may become different taking the charged groups on the surface of GO into consideration. GO cannot penetrate from aqueous phase into lipid bilayer spontaneously by MD simulations. Because it is much amphiphilic, GO prefers to stay at the interface between water and lipid headgroups. However, GO can still insert the membrane by cell’s endocytosis. We therefore initially put the GO in the center of membrane and then release it. Interestingly, it was found that several lipids were pulled out of the membrane to the surface of GO, resulting in the pore formation and water molecules flowing into the membrane. These findings offer a possible mechanism for the molecular basis of GO’s cytotoxicity and antibacterial activity.