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.

项目概要： 物理机械过程对于胚胎及其器官的形态发生至关重要。这 该提案的目标是对收敛扩展的机制进行多尺度分析，确定 建立被动组织特性（例如硬度和主动特性）的生物力学机制 产生延伸力、调节细胞行为和组织变形的过程，以及如何被动地 力学和主动力产生过程在青蛙胚胎内协调。研究概述于 该提案将回答：（1）细胞皮层力学和细胞形状的分子调节因子是什么 背轴伸长过程中的变化？我们之前将“机械成熟”的一种形式确定为细胞 从未分化的祖细胞向早期外胚层、中胚层或内胚层细胞的转变。为了回答这个问题 问题我们将确定调节因子并测试它们在细胞皮层密度和细胞形状、弹性和力方面的作用 生产。 (2)从早期伸长到晚期伸长，力的产生是如何协调的？模拟和实时成像 表明各向异性组织张力和细胞骨架极化之间存在协同作用，“细胞骨架 为了回答这个问题，我们将量化肌动球蛋白动力学的紧急聚焦并测试作用 用于肌动蛋白聚合和伸长中的肌球蛋白运输。 (3) 机械应变能的作用是什么 维持收敛延伸？初步数据揭示背侧存在“机械记忆” 组织在会聚伸展过程中存储和使用机械应变能。该目标将量化 机械记忆和应变能损失的作用，例如轴伸长时的应变能耗散。结果 该项目将补充正在进行的确定形态发生分子调节剂的努力 提供概念框架，开发形态发生和生物工程工具的新假设 测试他们。我们工作的意义使研究人员能够更全面地了解 细胞和组织力学对发育的贡献，了解组织力学在发育中的作用 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。