(312e) Molecular Simulation of Fibronectin Adsorption On Polyurethane Surfaces

Polyurethanes are very attractive class of polymers as biomaterials due to their relatively good biocompatibility and their excellent physical and mechanical properties. In this molecular simulation study we used fibronectin type I protein as a representative biological molecule to understand interactions between polyurethane surfaces and proteins. For this purpose, we examined the fibronectin adsorption behavior on two different polyurethane copolymer surfaces: Crystalline poly(ethylene glycol) + hexamethylene diisocyanate copolymer (PEG-HDI) and amorphous castor oil + hexamethylene diisocyanate copolymer (CO-HDI).

The simulations were carried out using the Accelrys Material Studio 4.1 package. First polyurethane matrices were constructed and structural properties such as d-spacing, radius of gyration, cohesive energy density and mechanical properties were estimated. These properties were in good agreement with available experimental data. Next, polymer surfaces were created and the fibronectin molecule was placed near polymer surfaces in six different orientations with each side of the fragments roughly facing the surface as described by Raffaini and Ganazzoli [1]. Simulations were carried out in an effective dielectric medium, and polymer surfaces were kept rigid. For each orientation, energy minimizations were carried out to analyze changes in the interaction energy between the surface and polymer due to adsorption, and the number of amino acids within a distance of 7 Å from the surface is determined. Next, a linear model was fitted to the interaction energy as a function of the number of amino acids. The slope in the model yielded the absolute interaction energies between the protein and the surface, and was used as a basis for the comparison of the surface biocompatibility, larger slope values indicating larger interaction strength.

Simulation results showed that fibronectin was adsorbed more strongly on PEG-HDI surface compared to CO-HDI surface, although the latter is less hydrophilic. This can be explained by the regular surface structure of crystalline PEG-HDI, allowing a better contact with the protein. Furthermore, the changes of phi and psi angles of the amino acids upon adsorption were also monitored in the simulations to determine the affinity of the amino acids to the surface. This information can be used to tailor polymer surfaces with functional groups to enhance protein adsorption.

References

[1] F.Ganazzoli, G. Raffaini, PCCP 7, 3651-3663 (2005).