血流下肝系细胞间粘附动力学及其对肝血窦组织功能的影响

Cell adhesion mediated by interactions between cell adhesive molecules and their ligands play key roles on blood perfusion and immune response in hepatic sinusoidal tissue. The adhesion dynamics between sinusoidal cells and blood cells, however, has been poorly quantified. The scientific issue in this project focuses on investigating the cell adhesion dynamics in sinusoidal tissue and corresponding molecular and micro-structural mechanisms. Upon the biomechanical approach that coordinates the advanced techniques of cellular and molecular biology, biomechanics, molecular simulation, and engineered in vitro tissue, the specific aims include: 1) determination of cell adhesion dynamics; 2) interplay between selectin and integrin receptors; 3) molecular binding kinetics and corresponding structural bases; and 4) engineered construction of in vitro three-dimensional sinusoidal tissue and cell adhesion dynamics. The goal of this project is to quantify the adhesion dynamics between sinusoidal cells and blood cells on mechanical and chemical regulation, to elucidate the binding kinetics and structural bases of β2 integrin-ICAM-1 interactions in specialized sinusoidal configuration and hepatic microcirculation, and to enlighten new idea in engineered hepatic tissue as well as for therapy of liver diseases.

细胞粘附分子与配体相互作用介导的细胞粘附动力学是调控肝血窦血流灌注和免疫应答的关键因素，但目前缺少对血窦组成细胞与血细胞间粘附动力学的定量研究。本项目针对肝血窦内不同细胞间粘附动力学及其分子机制和微观结构基础这一科学问题，结合细胞-分子生物学、生物力学、分子模拟、体外模型组织构建等实验技术与方法，开展以下研究：1）细胞粘附动力学；2）选择素-整合素交互作用；3）分子反应动力学及结构基础；4）肝血窦体外三维模型组织与粘附动力学。预期目标是定量认识血窦组成细胞与血细胞间粘附动力学特征以及力学、化学因素调控规律，重点理解β2整合素-ICAM-1相互作用介导细胞粘附的反应动力学及微观结构机制，为认识肝血窦特异结构的生物学功能、阐明肝脏微循环分子机制提供基础数据，并为肝脏组织工程化构建、肝脏疾病治疗提供新思路。

细胞粘附分子与配体相互作用介导的细胞粘附动力学是调控肝血窦血流灌注和免疫应答的关键因素，但目前缺少对血窦组成细胞与血细胞间粘附动力学的定量研究。本项目针对肝血窦内不同细胞间粘附动力学及其分子机制和微观结构基础这一科学问题，结合细胞-分子生物学、生物力学、分子模拟、体外模型组织构建等实验技术与方法，开展了以下四方面研究：1）细胞粘附动力学；2）选择素-整合素交互作用；3）分子反应动力学及结构基础；4）肝血窦体外三维模型组织与粘附动力学。本项目圆满完成了预设目标，定量认识了血窦组成细胞与血细胞间粘附动力学特征以及力学、化学因素调控规律，探索了β2 整合素-ICAM-1 相互作用介导细胞粘附的反应动力学及微观结构机制，为认识肝血窦特异结构的生物学功能、阐明肝脏微循环分子机制提供基础数据，并为肝脏组织工程化构建、肝脏疾病治疗提供新思路。本项目已发表论文12篇，获得国家发明专利授权4项，出版专著章节1章，培养博士生10名，博士后1名。