基底刚度与表面纳米形貌对细胞粘附影响机理研究

项目名称： 基底刚度与表面纳米形貌对细胞粘附影响机理研究

项目编号： No.11272015

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 数理科学和化学

项目作者： 熊春阳

作者单位： 北京大学

项目金额： 90万元

中文摘要： 细胞与胞外基质（extracellular matrix）之间的粘附在细胞感知外界环境的过程中扮演关键角色。目前已知基底刚度和表面纳米形貌能够调控细胞粘附动态，但两者在此过程中的耦合作用机制仍不清楚。本项目拟采用弹性模量可调的生物相容性材料并结合纳米加工技术，制作具有不同刚度和表面纳米结构的培养基底，考察基底刚度和表面纳米形貌特征对于细胞粘附行为的耦合影响;由细胞粘附结构的微观力-化学平衡关系出发，建立两种因素协同作用于细胞粘附过程的分析模型，基于蒙特卡洛模拟方法，探究其内在统一的微观生物物理机制；结合相关生物学实验，探索细胞感知基底刚度和表面纳米结构过程中可能的胞内生化信号转导通路。本项目的结果将有望为体内种植材料和组织工程支架材料的优化设计提供理论分析依据和模型。

中文关键词： 细胞；生物材料；刚度；纳米理化性质；细胞外基质

英文摘要： Cell-matrix interfacial adhesions are crucial for many biological functions and processes, which also play a key role in cell sensing microenvironment. While both substrate stiffness and surface nanotopographic property have been approved capable of regulating cell adhesion, the coordination of their effects on the formation and kinetics of cell-matrix adhesion, from an experimental viewpoint, is far from being understood. The underlying biophysical mechanism of how substrate stiffness and surface characteristics co-act with each other in mediating cell adhesion still remains elusive. This project aims to quantitatively study the influence of substrate with tunable stiffness and nanostructured surface on cell adhesion. By means of nanolithography, a type of soft polymeric material as cell culture substrate will be fabricated, onto which the nanoislands with different size are replicated from etched Si molds. Also, the Young's modulus can be controlled via changing the ratios of curing agent to the monomer of the polymer. Combined with visualization of some key proteins involved using immunofluorescence labeling, dynamic features of cell-substrate adhesion will be monitored to investigate in response to extracellular environment with different rigidity and roughness. Particularly, cell adhesion strength will be m

英文关键词： Cell；Biomaterial；Stiffness；Nano physicochemical properties；Extracellular matrix