多配体-受体相互作用广泛存在于各细胞活动中，理解其在分子尺度上相互识别、结合以及其定量关系，对于阐明生命过程、疾病发病机制、药物开发等有着重要意义。基于原子力显微镜的单分子力谱技术极大地推动了单配体-受体相互作用的研究，然而由于传统探针修饰方法的限制，无法精确控制目标分子在探针上的数量及种类，进而难以开展分子尺度上的多配体-受体研究。本项目基于DNA纳米技术开发一种可寻址可定位的新型智能单分子力谱探针，提出一种普适性的多配体-受体相互作用分子机制探索的方法学研究。同时将针对两种典型的多配体-受体相互作用体系---核酸适配体-凝血酶和ephrin-A/ephrin-B配体- EphA4受体---对比研究来探索细胞信号传导和调控相关的多配体-受体相互作用的分子机理。本项目的顺利实施会对配体-受体的基础研究、以及药物开发、免疫治疗等生物医学应用提供基础理论和技术依据。

Multivalent ligand-receptor interactions exist widely in various cellular activities, and their recognition, binding and quantitatively relations are quiet important for elucidation of life processes, disease pathogenesis, drug development and so on. Single molecule force spectroscopy technology based on atomic force microscope has greatly promoted the studies of single ligand - receptor interactions. However, due to the limitations of conventional probe modification, it’s challenging to precisely control different number and specices of target molecules on the probe, and thus impossible to carry out multivalent ligand-receptor interactions on single molecule lever. The project will develop a new smart DNA-nanotechnology-based addressable targetable single molecule force spectroscopy probe, which would open an new method to explore the molecular mechanism of universal multivalent ligand-receptor interactions. At the same time, comparative studies on two typical multivalent ligand-receptor interactions --- aptamers-thrombin and ephrin-A/ ephrin-B-EphA4 --- will be conducted to explore their molecular mechanism on cellular signal transduction and regulation. The successful implementation of this project would provide basic fundamental knowledge on ligand-receptor research, and push technical developments on biomedical applications, e.g. drug development immunotherapy and so on.