Biomechanics of Morphogenesis

形态发生的生物力学

• 批准号: 10539423
• 负责人: LANCE A. DAVIDSON
• 金额: $ 50.84万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10539423
• 关键词: Actins; Actomyosin; Affect; Anatomy; Biological; Biomechanics; Biomedical Engineering; Biophysics; Cell Shape; Cells; Cellular biology; Complement; Coupling; Cues; Cytoskeleton; Data; Defect; Development; Developmental Biology; Disease model; Dorsal; Drosophila genus; Ectoderm Cell; Elasticity; Embryo; Endoderm Cell; Epithelial; Event; Exposure to; Failure; Fibrosis; Future; Generations; Germ Layers; Goals; Image; Instruction; Lead; Malignant Neoplasms; Measures; Mechanics; Memory; Mesoderm Cell; Microsurgery; Molecular; Molecular Biology Techniques; Morphogenesis; Movement; Myosin ATPase; Organ; Organogenesis; Pathway interactions; Phenotype; Process; Production; Property; Proteins; Rana; Regulation; Research Personnel; Role; Shapes; Signal Pathway; Structure; Techniques; Testing; Tissue Engineering; Tissues; Undifferentiated; Work; animal model development; biophysical techniques; cell behavior; cell cortex; convergent extension; density; gastrulation; genetic analysis; human disease; insight; knock-down; mechanical behavior; mechanical force; mechanical properties; multidisciplinary; polarized cell; polymerization; progenitor; protein complex; self assembly; simulation; success; tool; transmission process; tumorigenesis; vertebrate embryos

Project Summary: Physical mechanical processes are central to the morphogenesis of embryos and their organs. The goal of this proposal is to apply a multi-scale analysis of the mechanics of convergent extension, identifying biomechanical mechanisms that establish passive tissue properties such as stiffness as well as active processes that generate forces of extension, regulate cell behaviors and tissue deformation, and how passive mechanics and active force generating processes are coordinated within the frog embryo. Studies outlined in this proposal will answer: (1) What are the molecular regulators of cell cortex mechanics and cell shape change during dorsal axis elongation? We previously identified a form of "mechanical maturation" as cells transition from undifferentiated progenitor to early ectodermal, mesodermal, or endodermal cell. To answer this question we will identify regulators and test their role in cell cortex density and cell shape to elasticity and force production. (2) How is force production coordinated from early to late elongation? Simulations and live-imaging suggest cooperativity between anisotropic tissue tension and polarization of the cytoskeleton, "cytoskeletal focusing". To answer this question we will quantify emergent focusing of actomyosin dynamics and test roles for actin polymerization and myosin transport in elongation. (3) What is the role of mechanical strain energy in sustaining convergent extension? Preliminary data reveals the existence of "mechanical memory" in dorsal tissues to store and use mechanical strain energy during convergent extension. This aim will quantify mechanical memory and the role of strain energy loss, e.g. strain energy dissipation in axis elongation. Results from this project will complement ongoing efforts to identify the molecular regulators of morphogenesis by providing a conceptual framework developing new hypotheses of morphogenesis and bioengineering tools to test them. The significance of our work provides researchers a more complete understanding of the contribution of cell- and tissue-mechanics to development, to understand the role of tissue mechanics in oncogenesis, and to provide fundamental physical principles for future functional tissue engineers.

项目总结： 物理机械过程是胚胎及其器官形态发生的核心。这个 这项建议的目标是应用多尺度分析收敛扩展的机制，确定 建立被动组织特性的生物力学机制，如僵硬和主动 产生伸展力、调节细胞行为和组织变形的过程，以及如何被动 力学和主动力量的产生过程在青蛙胚胎中是协调的。中概述的研究 这一建议将回答：(1)什么是细胞皮质力学和细胞形状的分子调节器 在背轴伸长过程中有变化吗？我们之前发现了一种“机械成熟”的形式，即细胞 从未分化的祖细胞过渡到早期的外胚层、中胚层或内胚层细胞。要回答这个问题 问题：我们将确定调节因子，并测试它们在细胞皮质密度和细胞形状中对弹性和力的作用 制作。(2)从早期伸展到后期伸展，力量生产是如何协调的？模拟和实时成像 提示各向异性组织张力和细胞骨架极化之间的协同作用 为了回答这个问题，我们将量化肌动球蛋白动力学和测试角色的紧急聚焦 用于肌动蛋白聚合和肌球蛋白在延伸过程中的运输。(3)机械应变能在其中起什么作用？ 保持融合扩展？初步数据显示背侧存在机械记忆 组织在收敛伸展过程中储存和使用机械应变能。这一目标将量化 机械记忆和应变能损耗的作用，例如应变能耗散在轴伸长中的作用。结果 该项目将通过以下方式补充正在进行的识别形态发生的分子调控因素的努力 提供了一个概念框架，开发了形态发生的新假设和生物工程工具 对他们进行测试。我们的工作的意义为研究人员提供了更全面的了解 细胞力学和组织力学对发育的贡献，以了解组织力学在 肿瘤发生，并为未来的功能组织工程师提供基本的物理原理。