Biomechanics of Morphogenesis

形态发生的生物力学

• 批准号: 9382714
• 负责人: LANCE A. DAVIDSON
• 金额: $ 39.27万
• 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: 2005-09-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9382714
• 关键词: Actomyosin; Affect; Anatomy; Apical; Architecture; Behavior; Biomechanics; Biomedical Engineering; Biophysics; Cell Cycle; Cell Shape; Cell Size; Cells; Cellular biology; Complement; Complex; Confocal Microscopy; Cues; Cytoskeleton; Defect; Dependence; Dependency; Development; Developmental Biology; Dorsal; Drosophila genus; Embryo; Epithelial; Event; F-Actin; Failure; Fibrosis; Foam Cells; Future; Generations; Germ Layers; Goals; Image Analysis; Lead; Malignant Neoplasms; Measures; Mechanics; Mesoderm; Microsurgery; Molecular; Molecular Biology Techniques; Morphogenesis; Movement; Neighborhoods; Organ; Organogenesis; Pathway interactions; Process; Production; Property; Proteins; Rana; Regulation; Research Personnel; Role; Shapes; Signal Pathway; Signal Transduction; Structure; System; Techniques; Testing; Thick; Tissue Engineering; Tissue Model; Tissues; Variant; Work; animal model development; base; biophysical techniques; cell behavior; convergent extension; embryo tissue; gastrulation; genetic analysis; human disease; insight; knock-down; mechanical properties; multidisciplinary; neural plate; novel strategies; physical process; planar cell polarity; polarized cell; protein complex; self assembly; success; theories; tool; 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) How are cell-scale structures and tissue mechanics are integrated during elongation? Early development is marked by dramatic changes in the mechanical properties of embryos. To understand how and why these properties change we test simple models of tissue mechanics based on synthetic closed-cell foams using bioengineering and biophysical methods to disrupt features from large scale architecture to the subcellular actomyosin-dependent cortex. (2) What single-cell mechanical processes contribute to convergent extension? We extend our analysis of cell behaviors to an unbiased approach that combines wide-field confocal microscopy with descriptive biomechanical analyses from the level of the cell, to the local neighborhood, to the strain fields of the entire embryo. Combining analyses of neural plate and paraxial somitic mesoderm we describe the dependence of these movements on planar polarity signaling. Using systems approaches we seek to test the dependencies of specific cell behaviors on both upstream signaling systems and their targeted downstream effectors. (3) How are tissue polarity cues transduced into polarized cell behaviors? We hypothesize that polarized cell behaviors and the oriented forces they generate are the result of cues produced by anisotropic strain. To test the roles of polarized intracellular factors and mechanical strain in organizing cell behaviors we use magnetogenetics and micro-scale tissue stretchers. 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 这项建议将回答：(1)细胞尺度的结构和组织力学是如何在 伸长？早期发育的标志是胚胎机械性能的戏剧性变化。至 为了了解这些特性如何变化以及为什么变化，我们测试了基于以下内容的组织力学简单模型 使用生物工程和生物物理方法来破坏大规模特征的合成闭孔泡沫 亚细胞肌球蛋白依赖的皮质的结构。(2)单细胞机械加工 有助于融合扩展？我们将我们对细胞行为的分析扩展到一种公正的方法，即 将广域共聚焦显微镜与细胞水平的描述性生物力学分析相结合， 从当地社区到整个胚胎的应变场。神经板和神经板的联合分析 近轴体细胞中胚层我们描述了这些运动对平面极性信号的依赖性。 使用系统方法，我们试图测试两个上游的特定细胞行为的相关性 信号系统及其目标下游效应器。(3)组织的极性线索是如何转化为 两极化的细胞行为？我们假设极化的细胞行为和它们产生的方向力 是各向异性应变产生的线索的结果。为了测试极化的细胞内因子和 在组织细胞行为的机械应变中，我们使用了磁遗传学和微尺度组织拉伸器。 该项目的结果将补充正在进行的识别形态发生的分子调控因素的努力。 通过提供开发形态发生和生物工程工具的新假说的概念框架 来测试他们。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。