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

CBET-0644968 Putnam该项目将研究毛细血管形态发生与细胞接种处细胞外基质力学之间的关系（三维）。这项研究将提供关于细胞外基质（ECM）力学对毛细血管形态发生影响的重要信息，并提供一个良好的三维环境，以研究力学在细胞行为（分化）中的作用。该项目将研究细胞力学和ECM力学对毛细血管形态发生的作用，在宏观尺度上使用荧光显微镜和切片，在分子尺度上使用肌球蛋白轻链磷酸化关键分子的抑制剂。 该研究将对组织工程领域产生很大的影响，提供有关组织工程支架血管化如何发生以及如何考虑材料刚度为组织工程支架开发更好的设计的信息。 从长远来看，拟议的研究活动的成功可以提高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。基于网络的模块有可能达到广泛的受众，是有价值的组织工程教学。

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.