间充质干细胞与液体界面的动态自适应反馈机制研究

干细胞与细胞外基质界面是一个动态自适应微环境，干细胞重塑细胞外基质的物理性质如刚性和纳米拓扑结构等，这些性质变化进而影响干细胞命运抉择。然而，现有生物材料设计不能充分模拟细胞外基质的动态适应性特征，干细胞与细胞外基质动态自适应力学反馈的具体机制尚不明晰。在前期工作基础上，本项目拟利用耗散型非平衡态自组装策略设计自适应仿生界面，构建基于液液界面自组装的蛋白质单层膜，模拟细胞外基质的自适应机械增强性质，主动平衡细胞内牵引力，进而增强间充质干细胞的力学信号转导。通过明晰间充质干细胞与液液界面自组装蛋白质单层膜的动态自适应反馈过程，揭示单层膜的自适应动态演变的分子机制，阐明基质的自适应动态性质与间充质干细胞的力学响应行为和干细胞命运之间的关系，最终实现间充质干细胞的离体自我更新和干性维持。研究结果不仅为调控干细胞行为和功能提供新的利器，还将为再生医学和组织工程中生物材料设计奠定良好的理论基础。

The interface between stem cell and extracellular matrix (ECM) is a dynamic adaptive microenvironment. Stem cells remodel the biophysical properties of ECM such as stiffness and nanotopological structure, and these biophysical cues further dictate stem cell fate. However, currently available biomaterials cannot emulate the native ECM with the dynamic adaptive characteristics. And it is unclear about the dynamic and mutually adaptive mechanism occurring between stem cell and the ECM. Based on our previous work, the applicant intends to design an adaptive bio-inspired interface using the dissipative non-equilibrium assembly strategy. Self-assembled protein monolayer on a liquid–liquid interface will be constructed, which can emulate the adaptive mechanical enhancement of native ECM. It can adapt to the cell traction force, and further enhance the mechanotransduction signals of mesenchymal stem cells. The applicant will clarify the dynamic and mutually adaptive process occurring between mesenchymal stem cells and liquid interfacially assembled protein monolayers, reveal the molecular mechanism of the adaptive dynamic evolution of protein monolayers, make clear the relationship between adaptive dynamic property of biomaterials and mechano-response behaviors and subsequent fate decisions of mesenchymal stem cells, and finally achieve in vitro self-renewal and stemness retention of mesenchymal stem cells. The results will provide a new tool to regulate stem cell behaviors and function, and lay a solid theoretical foundation for the development of next-generation biomaterials for regenerative medicine and tissue engineering.