基于生物热力学方法的功能化氧化石墨烯与蛋白质相互作用机制研究

The biological effects of graphene nanomaterials is solved one of the topics at the forefront. In this project, the multiple functionalized graphene oxide (GO) are selected as the object of research and the important proteins in the plasma are used as biological models. The thermodynamics and kinetic properties of their interaction are investigated by using modern microcalorimetric technique, spectroscopic methods, electrochemical methods, transmission electron microscopy and biochemical analysis techniques. The influence of the interaction mechanisms, which affected by GO with different structure and different surface modification, are investigated systematically on the structure and function. Furthermore, the structure-activity relationship between GO and proteins will be established, and some important thermodynamic parameters and kinetic parameters will also be obtained. The influences of GO component, size, morphology, aggregation state, surface structure, and the molecular structure of the proteins on the thermodynamic and kinetic properties will be investigated. The order of affinities of proteins to each kind of GO in a certain structure will be found out and expressed by thermodynamic parameter such as the interaction equilibrium constants, and the order of competing interaction rates will also be found and expressed by using the kinetic parameters. Comprehensive thermodynamic and kinetic research on each kind of GO will be performed for the interaction processes of various proteins. The influence path and the molecular mechanism of the structure of proteins affected by GO will be revealed deeply, and the mechanism of GO involved in the biochemical process will be further understood and revealed. The novel method of GO biological effects will be developed. These research will provide quantitative data and theoretical basis for design of GO and for thorough application of GO in biomedical fields.

石墨烯等纳米材料的生物效应是当前亟待解决的前沿课题之一。本项目以系列功能化氧化石墨烯为主要对象，将宏观和微观研究手段相结合，采用生物微量热、光谱学、电化学、显微成像和生化分析技术，从热动力学角度出发，在生物大分子水平上，从结构和功能上系统研究不同结构、不同表面性质的氧化石墨烯与血浆中重要蛋白质的相互作用机制；获取相关作用的热力学和动力学参数，并探讨氧化石墨烯组成、尺寸、形态、聚集状态及表面结构等因素及蛋白质分子结构对热力学和动力学性质影响，及其规律性；利用热力学参数表达其蛋白冠的稳定性，获取其对不同蛋白质的亲和性强弱顺序；深入探讨氧化石墨烯对蛋白质结构的影响途径及其作用分子机制，进一步揭示和认识氧化石墨烯参与生命动态化学过程的机制；建立基于生物热力学的氧化石墨烯生物效应研究的新方法，为氧化石墨烯等纳米材料的设计及其在生物医学领域的深入应用提供定量数据和理论依据。

石墨烯等纳米材料的生物效应是当前亟待解决的前沿课题之一。本项目以功能化氧化石墨烯为主要对象，将宏观和微观研究手段相结合，采用生物微量热、光谱学、电化学、显微成像和生化分析技术，从热动力学角度出发，在生物大分子水平上，从结构和功能上系统研究不同结构、不同表面性质的氧化石墨烯与血清重要蛋白质的相互作用机制。实验结果表明，氧化石墨烯与血清中重要蛋白质以摩尔比为1：1结合形成新的基态复合物，氧化石墨烯能静态猝灭蛋白质的内源荧光。氧化石墨烯可改变蛋白质的二级和三级空间结构，进而降低蛋白质的稳定性和生物功能。这些结果可促使人们在分子水平上对氧化石墨烯参与生命动态化学过程的机制有更全面的认识，为氧化石墨烯等纳米材料的设计及其在生物医学领域的深入应用提供定量数据和理论依据。该项目的相关研究工作共发表SCI源刊论文17篇，其中影响因子>3.0的6篇，获授权国家发明专利5项。