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.

项目摘要： 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机制进行多尺度分析，确定 建立被动组织特性（例如刚度和活性）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 力学和主动力生成过程在青蛙胚胎中进行协调。概述的研究 该提案将回答：（1）如何整合细胞尺度结构和组织力学。 伸长？早期发育的特征是胚胎的机械性能发生了巨大变化。到 了解这些特性如何以及为什么会改变我们基于组织力学模型的简单模型 使用生物工程和生物物理方法的合成闭孔泡沫，以大规模破坏特征 对亚细胞肌球蛋白依赖性皮质的结构。 （2）哪些单细胞机械过程 有助于收敛扩展？我们将对细胞行为的分析扩展到一种公正的方法 将宽视野共聚焦显微镜与描述性生物力学分析相结合，从细胞的水平到 当地的社区，到整个胚胎的应变场。结合神经板的分析和 近期的躯体中胚层我们描述了这些运动对平面极性信号传导的依赖性。 使用系统方法，我们寻求测试两个上游特定细胞行为的依赖性 信号系统及其目标下游效应子。 （3）如何转导到组织极性提示 极化细胞行为？我们假设它们产生了极化的细胞行为及其定向力 是各向异性菌株产生的提示的结果。测试极化细胞内因子和 组织细胞行为中的机械应变我们使用磁化遗传学和微尺度组织担架。 该项目的结果将补充持续的努力来识别形态发生的分子调节剂 通过提供一个概念框架，开发了形态发生和生物工程工具的新假设 测试它们。我们工作的意义使研究人员对 细胞和组织力学对发育的贡献，了解组织力学在 肿瘤发生，并为将来的功能组织工程师提供基本的物理原理。