CAREER: Physical Shaping of Multicellular Mesenchymal Tissues

职业：多细胞间充质组织的物理塑造

• 批准号: 0845775
• 负责人: Lance Davidson
• 金额: $ 50万
• 依托单位: University of Pittsburgh
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0845775&HistoricalAwards=false
• 关键词: CAREER; Physical; Shaping; Multicellular; Mesenchymal

During early development mesenchymal cells migrate, rearrange, and change shape to remodel the embryo. Coordinated movements of loosely-packed mesenchymal cells in the early embryo construct the vertebrate body plan and populate tissues in preparation for the construction of muscles, connective tissue and bone, as well as the lymphatic and circulatory systems. Many genes and many cells participate in these events, but there is little experimental evidence on how genes and cells generate physical forces and integrate biochemical pathways to drive mechanical movements within embryos. The goal of this research is to investigate how genes control the physical mechanics of multicellular mesenchymal tissues by: 1) analyzing the physics of re-aggregation and the cellular mechanics responsible for rapid phases of tissue sculpting, 2) challenging cells with varied micro-environments and assessing how their behavior changes, and 3)vary levels of cell adhesion molecules and surface contractility to reveal how mesenchymal tissue spreading and engulfment are mechanically coordinated. Understanding the molecular basis of rules governing the ordered assembly of mesenchymal tissue will explain how events at the subcellular scale coordinate cell behaviors during assembly of organs and functional tissues. These findings will complement and extend efforts to understand the molecular basis of mesenchymal morphogenesis and begin the process of integrating the molecular machinery into larger "morphogenetic" processes that are robust and may be adapted by tissue engineers. The cross- and interdisciplinary training resulting from this project will provide biologists and tissue engineers the ability to integrate learned concepts into a framework the will be important for both fields.

在早期发育过程中，间充质细胞迁移、重排和改变形状以重塑胚胎。早期胚胎中松散堆积的间充质细胞的协调运动构建了脊椎动物的身体计划和填充组织，为肌肉、结缔组织和骨骼以及淋巴和循环系统的形成做准备。许多基因和许多细胞参与了这些事件，但很少有实验证据表明基因和细胞如何产生物理力量并整合生化途径来驱动胚胎内的机械运动。本研究的目的是研究基因如何控制多细胞间质组织的物理力学：1)分析重聚集的物理学和组织雕刻快速阶段的细胞力学；2)在不同的微环境下挑战细胞并评估其行为如何变化；3)不同水平的细胞粘附分子和表面收缩性以揭示间质组织的扩散和吞噬是如何机械协调的。了解间充质组织有序组装规则的分子基础，将解释亚细胞尺度上的事件如何协调器官和功能组织组装过程中的细胞行为。这些发现将补充和扩展理解间充质形态发生的分子基础的努力，并开始将分子机制整合到更大的“形态发生”过程中，这些过程是强大的，可能被组织工程师所适应。这个项目带来的交叉和跨学科的培训将为生物学家和组织工程师提供将所学概念整合到一个框架中的能力，这对两个领域都很重要。