CAREER: Defining the Biomechanical Role of the Extracellular Matrix in Capillary Morphogenesis: An Interdisciplinary Plan Integrating Research and Education

该项目将研究毛细血管形态发生与细胞播种的细胞外基质力学之间的关系（三维）。该研究将为研究细胞外基质（ECM）力学对毛细血管形态发生的影响提供重要信息，并为研究力学在细胞行为（分化）中的作用提供一个良好的三维环境。该项目将在宏观尺度上使用荧光显微镜和切片技术研究细胞力学和ECM力学在毛细血管形态发生中的作用，在分子尺度上使用抑制剂来抑制肌球蛋白轻链磷酸化的关键分子。该研究将对组织工程支架的血管化如何发生以及如何更好地设计考虑材料刚度的组织工程支架提供信息，从而对组织工程领域产生重大影响。从长远来看，该研究活动的成功将增强对内皮基质在毛细血管形态发生中的机械作用的理解，这将对人类疾病的研究和治疗产生影响。该项目有五个不同的教育目标，涉及研究生、本科生、高中生和中学生的组织工程学习。一个重要的目标是开发在线网络模块，其中包含由本科生和研究生生成的实验室演示视频。基于网络的模块具有广泛受众的潜力，对组织工程教学有价值。

CBET-0644968 Putnam The project will investigate the relationship between capillary morphogenesis and the mechanics of the extracellular matrix where the cells are seeded (in three dimensions). The research will provide important information on the influence of extracellular matrix (ECM) mechanics on capillary morphogenesis and provide with a well characterized three-dimensional environment where to study the role of mechanics in cellular behavior (differentiation). The project will study the role of cell mechanics and ECM mechanics on capillary morphogenesis at the macroscale using fluorescence microscopy and sectioning and at the molecular scale using inhibitors to key molecules in the myosin light chain phosphorylation. The research will have a high impact to the field of tissue engineering by providing information on how vascularization of tissue engineering scaffolds can occur and how better designs can be developed for tissue engineering scaffolds taking into account the stiffness of the material. In the long term, the success of the proposed research activity could enhance the understanding of the endothelial matrix's mechanical role in capillary morphogenesis, which will have impact in the study and treatment of human diseases.The project has five different educational objectives and involves graduate, undergraduate, high school and middle school students in tissue engineering learning. One important goal is to develop on-line web modules that contain video of laboratory demonstrations generated by undergraduate and graduate students. The web based modules have the potential to reach wide audiences and are valuable to tissue engineering teaching.