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.

项目摘要： 物理机械过程是胚胎及其器官形态发生的核心。的 本提案的目标是对收敛扩展机制进行多尺度分析， 生物力学机制，建立被动组织性质，如刚度以及主动 产生伸展力的过程，调节细胞行为和组织变形，以及如何被动 力学和主动力产生过程在青蛙胚胎内协调。概述的研究 这一建议将回答：（1）什么是细胞皮层力学和细胞形状的分子调节因子 在背轴伸长过程中的变化？我们以前确定了一种形式的“机械成熟”的细胞 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。回答这个 问题，我们将确定监管机构和测试他们的作用，在细胞皮层密度和细胞形状的弹性和力量 生产(2)从早伸长到晚伸长，力的产生是如何协调的？模拟和实时成像 提出了各向异性组织张力和细胞骨架极化之间的协同性，“细胞骨架 聚焦”。为了回答这个问题，我们将量化肌动球蛋白动力学和测试作用的紧急聚焦 肌动蛋白聚合和肌球蛋白运输的延伸。(3)机械应变能在 持续收敛扩张初步数据揭示了背侧神经元存在“机械记忆”。 组织在会聚伸展期间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失的作用，例如轴伸长中的应变能耗散。结果 从这个项目将补充正在进行的努力，以确定分子调控的形态发生， 提供一个概念框架，发展形态发生和生物工程工具的新假设， 测试他们。我们工作的意义为研究人员提供了一个更完整的了解， 细胞和组织力学对发育的贡献，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。