血流剪切环境下E-选择素-CD44相互作用是炎症反应中介导白细胞在血管内皮细胞表面慢速滚动粘附的关键分子体系，E-选择素-CD44相互作用一方面促进白细胞表面PSGL-1-L-选择素之间的簇集，进而增强通过PSGL-1胞内信号通路激活β2整合素的能力；另一方面也可以独立启动CD44胞内信号通路激活β2整合素。但是其双重身份的内在机制不清楚。本项目以E-选择素-CD44相互作用体系为对象，以其信号转导机制为科学问题，拟开展以下研究：1）E-选择素-CD44相互作用微观结构特征及外力调控；2）E-选择素-CD44相互作用反应动力学及力学调控；3）血流剪切下E-选择素-CD44相互作用介导的白细胞粘附动力学；4）E-选择素调控CD44胞内信号通路特征及力学依赖性。本项目采用“宏观”与“微观”、“现象”与“机制”相结合的研究思路为深入阐释其生物学功能提供数据。

E-selectin-CD44 interactions play key roles in inflammation cascade by modulating the slow rolling of leukocyte on endothelium under blood shear flow. On the one hand, E-selectin-CD44 interactions enhance clustering of PSGL-1 and L-selectin and followed activation of β2 integrin through PSGL-1 intracellular signal pathway; On the other hand, they can also activate β2 integrin directly through CD44 intracellular signal pathway. The intrinsic molecular mechanism of their dual function remains unclear. The scientific issue of this project focuses on elucidating the signal transduction mechanism of E-selectin-CD44 interactions in inflammation cascade. Four aims are included: 1) Predict micro-structural features of E-selectin-CD44 interactions and the impact of external force; 2) Quantify molecular binding kinetics of E-selectin-CD44 interactions and the impact of external force; 3) Quantify cellular adhesion dynamics modulated by E-selectin-CD44 interactions under different blood shear flow; 4) Clearify the force-dependent signal transduction pathway of E-selectin-CD44 interactions. Upon the combinations of “macro” and “micro”, “phenomenon” and “mechanism”, the goal of this project is to deepen the understanding of biological function.