Research On Adsorption Mechanism Of Rgd On TiO₂ Surfaces With Nanostructure

Titanium and titanium alloy are extensively used for bio-medical metal materialsdue to their excellent corrosion resistance, biocompatibility, bone fusion and biologicalfunctionality. Surface properties, such as surface structure and surface roughness, of im-plant affect cell adhesion, proliferation and differentiation, finally determine the quality oftissue growth and therefore are important factors which directly in?uences the success ofimplant. A micro-roughness of less than 10 nm contains material defects themselves andnanostructures which are active regions for adsorption and further affect the integrationbetween biomolecule and implant surface. By use of molecular dynamics (MD) method,this paper study the motion characteristic of biomolecule and investigate the effect mech-anism of the surface nanostructures of Ti-materials on RGD and protein adsorption at theatom scale. These researches have important theoretical meanings and real value in thefurther acquaintance of adsorption mechanism of protein and cell on the Ti-biomaterialsurface, and provide theoretical basis for designing the surface structure of titanium im-plants and peptide pattern to promote cell adhesion.Firstly, the TiO₂ adsorption substrates with nanostructure are set up, and the for-mula for Gibbs surface energy are modified in accordance with the slab model of MDsimulations in order to evaluate the surface energies of complex large-scale topographysurface. The studies on surface strcture and surface energy of TiO₂ surface substratesindicate: the substrate model with more than four, two, two and one layers away from thefixed layer describes well the surface characteristics of rutile (110), anatase (101), (100)and (001) surface, respectively; the nanostructure edges expose more undercoordinated,unstable, dangling-bond atoms, and the more highly undercoordinated atoms exhibit thelarger displacement vectors; surfaces with more highly coordinated atoms are lower inenergy than surfaces exhibiting undercoordinated atoms, and surface energies of surfaceswith nanostructure are higher than those of perfect surfaces; in order to obtain a highersurface energy, for rutile (110) surface, the horizontal direction along which atoms are cutout should be chosen in accordance with nanostructure sizes: [110] direction for a smallnanostructure size and [001] direction for a big nanostructure size, or alternatively atomsare removed along [110] direction to increase the depth of nanostructure; for anatase (101) surface, surface energy increases sharply with increasing nanostructure depth within 1 nm.Secondly, the adsorption models of RGD on TiO₂ surfaces with nanostructure inMD simulations are set up, the adsorption conformation and adsorption mechanism ofRGD on rutile TiO₂ surface are studied, and the effect of surface nanostructure and wa-ter molecule on RGD adsorption is discussed. It is shown that: water molecules reachfirst the hydrophilic TiO₂ surface and occupy adsorption sites, i.e., water oxygen atomsbond to surface titanium atoms to form the stable first hydration layer and interact withsurface oxygen atoms to form the second hydration layer; the adsorbed water layers alsoplay an intermediary role as they form hydrogen-bond interactions with the hydrophilicgroups of RGD, which is helpful to RGD adsorption on TiO₂ surfaces; the guanido groupC(NH₂)₂⁺, amino groups NH₃⁺ and carboxyl group COO^- of RGD bond to TiO₂ surfaceby electrostatic and van der Waals interactions. On the perfect surface, since the fivefoldtitanium atom is surrounded by surface bridging oxygen atoms above it and has a watermolecule bonding to it, the guanido group is the adsorption group. However, because thesurface with nanostructure exposes more adsorption sites and has higher surface energy,RGD can adsorb rapidly on the surfaces by guanido group and amino groups, and thecarboxyl group may also edge out the adsorbed water molecules and bond to the surfacetitanium atom. It is also demonstrated that RGD adsorbs much more rapidly and stably onthe surface with nanostructure than the perfect surface. Moreover, the surface with highersurface energy has more adsorption energy of RGD.Finally, the adsorption of RGD-containing fibronectin (FN) on TiO₂ surface is stud-ied further by MD simulations, the adsorption models of protein on TiO₂ surfaces are setup, the equilibrium condition of protein simulation is discussed, the adsorption mecha-nism of protein and the effect of different orientation, nanostructure, surface energy andwater molecule on FN adsorption are analyzed, and the FN preferential orientation of celladhesion is provided. The simulation results show that system potential, protein RMSDand radius of gyration tend to certain values, which indicates that the simulation time ofnanosecond order can express well the adsorption of protein on TiO₂ surfaces with nanos-tructure. Protein FN-III10 in aqueous solution binds to TiO₂ surface through charged po-lar amino acids whose second structure isβ-turn or coil. For hydrophilic TiO₂ surfaces inaqueous solution, due to the distribution form of surface atom, the perfect surfaces bindto protein only by surface bridge oxygen and water; while the surfaces with nanostruc- ture having higher surface energy expose more undercoordinated dangling-bond atoms toform more adsorption sites, thus it is possible for them to bind to protein by other types,such as Tis–OH₂···O_COO^--FN and Tis–O_COO^--RGD. Surfaces with nanostructure havinghigher surface energy, especially deep pit surface, can greatly promote the rapid and sta-ble adsorption of protein FN-III10 on TiO₂ surfaces by many groups. Considering thewhole FN structure and the site of sequence ARG78-GLY79-ASP80 (RGD, cell adhesionsite) on surface after protein adsorption, orientations X90, X180 and X270 of FN-III10are best for the reason that they have higher adsorption energy, adsorb stably and rapidly,and are helpful to cell adhesion.