循环血流中，血小板CD40L的分泌、聚化与功能的力学调控机制

在血流动力学环境中，血小板和白细胞受粘附与趋化因子的介导而发生相互作用，协同调节冠脉斑块的早期形成和发展及斑块破裂后的血栓形成。血小板细胞类趋化因子CD40L是介导血小板与白细胞相互作用的关键分子。本项目，针对CD40L在力学微环境中的分泌、构象与功能演化这一前沿科学问题，拟综合运用分子生物学、细胞分子生物力学等的理论原理、实验技术和分析方法，结合原子力显微镜、激光共聚焦显微镜、荧光显微、流动腔与分子动力学模拟等技术手段，开展系统深入的研究。力图阐明力是如何调节CD40L的分泌、聚合、构象与功能的，揭示CD40L与受体（CD40、αIIbβ3、 Mac-1和α5β1）相互作用的力学调控机制与分子结构基础，探明CD40L介导的血小板-白细胞接触面的形成与演化的力-化学协同调控机制。旨在更加深理解心脑血管疾病的生理病理过程，为心脑血管疾病患者的临床治疗和康复与药物设计提供新思路

In the hemodynamic environment, circulating platelets and white blood cells will interact with each other under mediating of some adhesive molecules and chemokine factors, be involved in the early formation and development of coronary plaque and thrombosis after plaque rupture. Platelet CD40L is a key molecule mediating the interaction between platelets and leukocytes. The research focus at the frontier scientific problem for events on the secretion, conformation and function evolution of CD40L in flows. We will carry out systematic and in-depth research on the events with the strategy which intends to integrate the theoretical principles, experimental techniques and analytical methods of molecular biology, cell and molecular biomechanics, and combine atomic force microscopy, laser confocal microscopy, fluorescence microscopy, flow chamber and molecular dynamics simulation. The aim of this study is to elucidate how CD40L regulates the secretion, aggregation, conformation transformation and functional change of CD40L, reveal the mechanical regulation mechanism and molecular basis of the.interaction between CD40L and its receptors (CD40, alpha IIbbeta 3, Mac-1 and alpha 5beta 1), and explore the mechano-chemical regulation mechanism of the formation and evolution of CD40L-mediated cell contact area between platelet and leukocyte, for understanding the physiological and pathological processes of cardiovascular and cerebrovascular diseases, and providing a solution for the clinical treatment and rehabilitation of patients with cardiovascular and cerebrovascular diseases, the discovery of related molecular drug targets and the novel design of antibody drugs.