Effects of atomic-level nano-structured hydroxyapatite on adsorption of bone morphogenetic protein-7 and its derived peptide by computer simulation

Qun Wang,Fuzeng Ren,Liming Fang,Guoming Lu,Kefeng Wang,Menghao Wang,Xiong Lu

doi:10.1038/s41598-017-15219-6

Abstract

Hydroxyapatite (HA) is the principal inorganic component of bones and teeth and has been widely used as a bone repair material because of its good biocompatibility and bioactivity. Understanding the interactions between proteins and HA is crucial for designing biomaterials for bone regeneration. In this study, we evaluated the effects of atomic-level nano-structured HA (110) surfaces on the adsorption of bone morphogenetic protein-7 (BMP-7) and its derived peptide (KQLNALSVLYFDD) using molecular dynamics and density functional theory methods. The results indicated that the atomic-level morphology of HA significantly affected the interaction strength between proteins and HA substrates. The interactions of BMP-7 and its derived peptide with nano-concave and nano-pillar HA surfaces were stronger than those with flat or nano-groove HA surfaces. The results also revealed that if the groove size of nano-structured HA surfaces matched that of residues in the protein or peptide, these residues were likely to spread into the grooves of the nano-groove, nano-concave, and nano-pillar HA, further strengthening the interactions. These results are helpful in better understanding the adsorption behaviors of proteins onto nano-structured HA surfaces, and provide theoretical guidance for designing novel bioceramic materials for bone regeneration and tissue engineering.

Highlights

Hydroxyapatite [HA, Ca10(PO4)6(OH)2] is the major inorganic component of bones and teeth
In order to obtain optimized geometries of bone morphogenetic protein-7 (BMP-7) and its derived peptide, a 20 ps energy minimization and a 1500 ps molecular dynamics (MD) relaxation in the water box were performed with a time step of 0.5 fs in the NPT ensemble using NAMD package[38]
BMP-7 was laid on the flat HA surface (Fig. 1d), which illustrated the interaction between BMP-7 and the flat HA surface before MD simulation

Summary

Introduction

Hydroxyapatite [HA, Ca10(PO4)6(OH)2] is the major inorganic component of bones and teeth. BMP-7 plays a crucial role in the induction and regulation of cartilage and bone formation and has an important influence on skeletal development and growth[25] This protein has been widely examined in previous studies. Tao et al.[33] prepared a new type of functional, self-assembling peptide nanofiber-hydrogel scaffold with the sequence RADKPS (ARG-ALA-ASP-LYS-PRO-SER); they clearly showed that RADKPS promoted cell proliferation and activity of human degenerative nucleus pulposus cells. Another peptide, KQLNALSVLYFDD (LYS-GLN-LEU-ASN-ALA-LEU-SER-VAL-LEU-TYR-PHE-ASP-ASP), is synthesized from the BMP-7 receptor I- and receptor II-binding active domains[31] and, in addition, has excellent osteogenic activity and induces mineralization of bone marrow stromal stem cells. These peptide molecules are small and the active sites can be exposed

Methods

Results

Conclusion