Interaction of biomolecules with anatase, rutile and amorphous TiO2 surfaces: A molecular dynamics study

The adhesion of biomolecules to dental and orthopedic implants is a fundamental step in the process of osseointegration. Short peptide motifs, such as RGD or KRSR, carried by extracellular matrix proteins or coated onto implant surfaces, accelerate cell adhesion and tissue formation. For this reason, understanding the binding mechanisms of adhesive peptides to oxidized surfaces of titanium implants is of paramount importance. We performed molecular dynamics simulations to compare the adhesion properties of 6 peptides, including the tripeptide RGD, its variants KGD and LGD, as well as the tetrapeptide KRSR, its variant LRSR and its truncated version RSR, on anatase, rutile, and amorphous titanium dioxide (TiO2) surfaces. The migration of these molecules from the water phase to the surface was simulated in an aqueous environment. Based on these simulations, we calculated the residence time of each peptide bound to the three different TiO2 structures. It was found that the presence of an N-terminal lysine or arginine amino acid residue resulted in more efficient surface binding. A pulling simulation was performed to detach the adhered molecules. The maximum pulling force and the binding energy were determined from the results of these simulations. The tri- and tetrapeptides had slightly greater adhesion affinity to the amorphous and anatase structure than to rutile in general, however specific surface and peptide binding characters could be detected. The binding energies obtained from our simulations allowed us to rank the adhesion strengths of the studied peptides.