本项目的主题内容是"细胞与胞外基质界面黏附：随机动力学与变形理论的耦合研究"，拟采用理论建模与计算模拟为主、结合必要实验的研究方式，发展完善已有的细胞黏附理论，建立受体-配体分子键团簇随机过程与连续介质变形的耦合体系，研究各类天然与人造胞外基质材料的理论与计算模型，探讨通过胞外基质的非均匀、多层次、各向异性、几何特征等力学设计实现细胞黏附的定量化调控。本课题的创新之处在于，从细胞黏附的分子组成结构出发，研究跨分子尺度的键分离与再键合随机过程、微米尺度的多分子键团簇动力学、(亚)细胞尺度的胞外基质变形与多黏附斑协同的耦合理论框架和计算方法，整个动力学过程涉及多个时间及空间尺度，是传统固体力学领域与生物学科交叉产生的科学问题。这项研究旨在为控制细胞的铺展、极化、迁移以及人造组织的设计、制备和检测提供完整直接的理论指导和方法支持，预期三年内发表高水平学术论文6-8篇。

In the proposal, we will study the coupled stochastic dynamics and deformation theory on interfacial adhesion between cell and extracellular matrix (ECM). A central paradigm of this research is development of theoretical and computational models, with experimental testing as a supplement, for improvement of the existing theories of cell-matrix adhesion. We will describe the stochastic dissociation and association processes of receptor-ligand bond clusters, establish the constitutive law of various natural and artificial ECM materials, unify stochastic reactions of individual bonds at molecular scale and elastic descriptions of interfacial interaction at continuum scale. The goal here is to explore the mechanical principles to quantitatively control cell adhesion via design and implementation in material heterogeneity, hierarchy, anisotropy and geometry. The innovation of this proposal is a bottom-up modeling strategy crossing molecular bonds, bond clusters, subcellular processes and continuum deformation. Theoretical approaches and numerical techniques including finite element analysis, Monte Carlo method, kinetic and stochastic dynamics will be utilized and developed to investigate the intrinsic spatial and temporal scales. The scientific issues are raised at the interface between traditional solid mechanics and rapidly advancing biological science. The study aims to provide a theoretical guidance and methodological support for quantitatively controlling dynamic cellular processes such as spreading, polarization and migration, and for enabling design, fabrication and testing of man-made ECMs. We expect to publish 6 to 8 papers in high-level journals within this 3-year project.