Surface-induced conformational and functional changes of bone morphogenetic protein-2 adsorbed onto single-walled carbon nanotubes.
Surface-induced conformational and functional changes of bone morphogenetic protein-2 adsorbed onto single-walled carbon nanotubes.
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DOI：
10.1016/j.bbrc.2013.09.036
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发表时间：
2013-10
影响因子：
3.1
通讯作者：
Ziyu Li;Qi Gan;Wenjing Zhang;Jing Zhang;Yuan Yuan-Yuan;Changsheng Liu
中科院分区：
文献类型：
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作者：
Ziyu Li;Qi Gan;Wenjing Zhang;Jing Zhang;Yuan Yuan-Yuan;Changsheng Liu
骨形态发生蛋白 2 (BMP-2) 在基质上的有效固定对于基于 BMP-2 的骨组织支架/植入物的开发至关重要。这通常与精确控制所需的蛋白质构象和保留蛋白质活性有关。最近，通过定制纳米级表面特性来调节蛋白质构象受到了极大的关注。在本论文中，我们以亲水性 COOH 和疏水性 CH3 封端的单壁碳纳米管（SWNTs-COOH 和 SWNTs-CH3）为模型，研究了纳米级界面诱导的重组人 BMP-2 (rhBMP-2) 的吸附动力学、构象和生物活性的变化。我们的数据表明，SWNTs-COOH和SWNTs-CH3快速结合并诱导rhBMP-2分子展开，促进其与细胞表面相应受体的相互作用，从而增强其生物活性。相比之下，rhBMP-2 对 COOH 封端的表面表现出比 CH3 基团封端更强的亲和力，同时更好地增强了 SWNTs-CH3 表面的生物活性。从SWNTs释放后，展开的rhBMP-2重新折叠，并且SWNTs-COOH和SWNTs-CH3的活性分别降低至天然rhBMP-2的90%和70%。基于获得的这些结果，提出了 rhBMP-2 与具有不同化学性质的 SWNT 的结合特征的模型。这项研究证明了简单定制的纳米级化学表面调节 BMP-2 的结合、构象和生物活性的可能性，从而允许制造具有高骨诱导性和低 BMP-2 剂量的基于 BMP-2 的骨组织支架。
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-CH3bound 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 CH3groups, while better enhanced bioactivity on the SWNTs-CH3surfaces. After released from SWNTs, the unfolded rhBMP-2 refolded and their activities from SWNTs-COOH and SWNTs-CH3were 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.