Collaborative Project: Physical Mechanisms of Morphogenesis

该提议的研究代表了一个名为“形态发生的物理机制”的合作项目。组织形态发生是机体及其各种器官的形态在胚胎中形成的过程，也是成年后引起伤口愈合、肿瘤侵袭等正常和异常变化的过程。该合作项目的两位项目负责人Stuart Newman（纽约医学院）和Gabor Forgacs（克拉克森大学）提议继续开展跨学科研究项目，研究组织的“一般”物理特性，如表面张力、界面张力和粘度，对组织的形态发生行为有重要影响。模型间充质组织包含悬浮细胞，或具有特定表面涂层的细胞大小的乳胶颗粒，将分析其表面和界面张力和粘度对基质的组成和大分子浓度的依赖性，以及悬浮细胞或颗粒的每体积数量和表面特性。模型矩阵中的界面驱动细胞运输（“矩阵驱动易位”）将被用作研究形态发生特性对物理和成分变量依赖的工具。来自禽类胚胎的活间充质组织混合或形成不混溶边界的能力，将与细胞外纤维网络的存在和这种网络的实验破坏有关。将开发一个理论框架来解释模型组织的物理、组成和微观形态之间的关系，以及它们形成界面、流动和表现出其他形态发生变化的能力。＊＊＊

9305628 Newman The proposed research represents a collaborative project entitled "Physical Mechanisms of Morphogenesis". Tissue morphogenesis is the process by which the form of the body and its various organs is established in the embryo, and by which normal and abnormal changes in the adult, such as wound healing and tumor invasion, are brought about. The two PIs on this collaborative project, Stuart Newman (New York Medical College) and Gabor Forgacs (Clarkson University) propose to continue a program of interdisciplinary studies on the idea that 'generic' physical properties of tissue, such as surface tension, interfacial tension, and viscosity contribute importantly to the tissue's morphogenetic behaviors. Model mesenchymal tissue containing suspended cells, or cell-sized latex particles with specific surface coatings, will be analyzed with respect to the dependence of their surface and interfacial tension and viscosity on the composition and macromolecular concentration of the matrix, as well as the number per volume and surface characteristics of the suspended cells or particles. Interfacially-driven cell transport in model matrices ('matrix-driven translocation') will be used as a tool to study the dependence of morphogenetic properties on physical and compositional variables. The ability of living mesenchymal tissue derived from avian embryos to mix, or to form boundaries of immiscibility, will be correlated with the presence of networks of extracellular fibers and the experimental disruption of such networks. A theoretical framework will be developed for interpreting the relationship among physical, compositional, and microscopic morphology of model tissues, and their capacity to form interfaces, to flow, and to exhibit other morphogenetic changes. ***