Computer simulations of fibronectin adsorption on hydroxyapatite surfaces

Abstract

The orientation and adsorption mechanism of the 10th and 7–10th type III modules of fibronectin (FN-III10, FN-III7–10) on hydroxyapatite surfaces were investigated by a combination of parallel tempering Monte Carlo (PTMC) and molecular dynamics (MD) methods. The PTMC results show a positively charged surface at low ionic strength is beneficial for FN-III10 and FN-III7–10 adsorption with RGD accessible in solution, i.e., FN-III10 adsorbs with “side-on” orientation while FN-III7–10 adsorbs with “lying” orientation. During the adsorption, FN-III10 adsorbs on the hydroxyapatite (HAP) surface first driven by Coulombic interactions at the pre-adsorption stage. At the post-adsorption stage, the driving force changes from Coulombic interactions to VDW interactions. Accordingly, slow translation of FN-III10 on the HAP surface was found due to the mismatching of charged groups of protein on the alternative charged surface. The conformational changes of adsorbed FN-III10 mainly take place at its coil/loop parts. FN-III7–10 experiences two stages from weak adsorption to strong adsorption when Coulombic interactions become the dominant driving force. The transition is determined by the anchoring of the basic residues in the Ca²⁺ vacancies by significant complementary electrostatic interactions and hydrogen bonds formed between the guanidine group and the surrounding phosphate groups. The module III10 of FN-III7–10 exhibits the largest conformational change and contributes to the adsorption most. The affinity of the guanidine group binding suggests that vacancies on biomaterials have the capacity to trap specific residues.