受体-配体反应动力学是细胞粘附的分子基础与决定因素，其在癌症侵袭转移过程中起着关键作用。在生理条件下，粘附蛋白分布具有多样性。粘附蛋白的分布变化可调控受体-配体键合与解离，势必对受体-配体相互作用及癌细胞的侵袭转移特性产生重要影响。然而，粘附蛋白的分布变化对受体-配体反应动力学的作用迄今尚不清楚。.本项目将针对均匀分布、随机分布与聚集分布三种典型的蛋白质分布类型，系统地研究膜上与基底中粘附蛋白的分布变化对受体-配体反应动力学的作用。实验研究粘附蛋白分布变化对受体-配体反应动力学参数——正、逆反应速率及亲和常数的影响。利用多尺度建模方法，结合统计力学理论，进一步研究蛋白质键合过程，阐明粘附蛋白分布变化对受体-配体反应动力学影响的物理调控机制，并建立定量描述蛋白质分布变化对受体-配体亲和常数影响的理论模型。本项目开展的工作对深化理解粘附蛋白分布的生物学功能、辅助指导药物设计与研发具有重要意义。

Receptor-ligand binding kinetics is the molecular basis and determinant for cell adhesion, and plays a key role in cancer metastasis. Under physiological conditions, there exist different types of distributions of adhesion proteins. The changes in the distribution of adhesion proteins will certainly have a significant impact on the receptor-ligand interactions and invasive and metastatic behaviors of cancer cell, since the receptor-ligand binding and unbinding depend strongly on the protein distribution. However, the effect of changes in the distribution of adhesion proteins on receptor-ligand binding kinetics is still unclear..In this project, we will systematically investigate the effect of changes in the distribution of cell membrane and substrate protein molecules on receptor-ligand binding kinetics for three typical types of distributions: uniform, random and clustered. An experimental study will be carried out to determine the effect of changes in the distribution of receptor and ligand molecules on their binding kinetic parameters including on- and off- rate, as well as binding constant. Further, we will investigate the receptor-ligand binding process and elucidate the physical mechanism underpinning the effect of changes in protein distribution on the receptor-ligand interactions based on the multiscale modeling and statistical mechanics methods. We aim to provide a quantitative description of the influence of changes in the protein distribution on the receptor-ligand binding constant by developing a theoretical model. Our work will contribute to deepening the understanding of the biological functions of protein distribution, and guiding the drug design and development.