Surface-induced conformational and functional changes of bone morphogenetic protein-2 adsorbed onto single-walled carbon nanotubes

Efficient immobilization of bone morphogenetic protein-2 (BMP-2) onto matrix is of crucial importance in the development of BMP-2-based bone tissue scaffold/implant. This often ties with precise control of desirable protein conformation and retention of protein activity. Recently, great attentions were paid to the regulation of protein conformation by tailoring the nanoscale surface properties. In this contribution, with hydrophilic COOH- and hydrophobic CH₃-terminated single-walled carbon nanotubes (SWNTs-COOH and SWNTs-CH₃) as models, we investigated the nanoscale interface-induced changes of adsorption dynamics, conformation, and bioactivity of recombinant human BMP-2 (rhBMP-2). Our data showed that SWNTs-COOH and SWNTs-CH₃ bound rapidly to and induced unfolding of rhBMP-2 molecules, which promoted their interactions with corresponding receptors on cell surface and thus enhanced their bioactivities. In contrast, rhBMP-2 showed stronger affinity to the COOH-terminated surface than that terminated with CH₃ groups, while better enhanced bioactivity on the SWNTs-CH₃ surfaces. After released from SWNTs, the unfolded rhBMP-2 refolded and their activities from SWNTs-COOH and SWNTs-CH₃ were reduced to 90% and 70% of the native rhBMP-2, respectively. Based on these results obtained, a model of the binding characteristics of rhBMP-2 onto SWNTs with different chemistry is presented. This study demonstrates the possibility of simple tailor-made nanoscale chemical surfaces to modulate the binding, conformation and bioactivity of BMP-2, allowing fabrication of BMP-2-based bone tissue scaffolds with high osteoinductivity and low BMP-2 dosage.