Biomechanics of Morphogenesis

形态发生的生物力学

基本信息

批准号：
10682477
负责人：
LANCE A. DAVIDSON
金额：
$ 40.66万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
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/10682477
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 Epithelium Event Exposure to Failure Fibrosis Future Generations Germ Layers Goals Image Malignant Neoplasms Measures Mechanics Memory Mesoderm Cell Microsurgery Molecular Molecular Biology Techniques Morphogenesis Movement Myosin ATPase Organ Organogenesis Pathway interactions Phenotype Polymers 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

项目摘要

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。概述的研究该建议将回答：（1）细胞皮质力学和细胞形状的分子调节剂是什么背轴伸长期间的变化？我们先前鉴定出一种“机械成熟”形式为细胞从未分化的祖细胞过渡到早期外胚层，中胚层或内皮细胞。回答这个问题我们将确定调节剂并测试其在细胞皮层密度和细胞形状中的作用到弹性和力生产。（2）从早期到晚延伸的力量生产如何协调？模拟和现场模仿提示各向异性组织张力与细胞骨架的极化之间的合作性，“细胞骨架重点”。为了回答这个问题，我们将量化肌动蛋白动力学的新兴聚焦和测试角色用于肌动蛋白聚合和肌球蛋白的伸长率。（3）机械应变能在维持收敛扩展？初步数据揭示了背面的“机械记忆” 在收敛延伸过程中存储和使用机械应变能的组织。这个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量耗散。结果从这个项目中将补充持续的努力，以确定形态发生的分子调节剂提供一个概念框架，开发出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。