Quantification and modeling of the emergence of tissue-level mechanics from individual cell heterogeneity

对个体细胞异质性组织水平力学的出现进行量化和建模

• 批准号: 9135441
• 负责人: SCOTT A HOLLEY
• 金额: $ 39.33万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-30 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9135441
• 关键词: 4D Imaging; Adhesions; Adhesives; Automobile Driving; Award; Behavior; Biological; Biological Assay; Cadherins; Calibration; Cell Adhesion; Cell Communication; Cell Density; Cell Volumes; Cell model; Cells; Characteristics; Code; Collecting Cell; Collection; Complement; Complex; Computer Analysis; Computer Assisted; Computer Simulation; Data; Data Analyses; Data Set; Defect; Development; Embryo; Embryonic Organizers; Ensure; Evolution; Exhibits; Fibronectin Receptors; Genetic; Growth; Health; Heterogeneity; Homeobox Genes; Image; Image Analysis; Individual; Label; Lasers; Length; Life; Liquid substance; Maintenance; Maps; Measurement; Mechanics; Methodology; Methods; Microscope; Microscopy; Modeling; Molecular; Monitor; Morphogenesis; Morphology; Motion; Musculoskeletal; Noise; Paraxial Mesoderm; Phenotype; Physics; Population; Positioning Attribute; Process; Property; Proteins; Publishing; Regulation; Research; Resolution; Role; Series; Signal Transduction; System; Systems Analysis; Tail; Time; Tissues; Travel; Vertebral column; Zebrafish; analytical tool; base; cell behavior; cell motility; cell type; cellular imaging; computer framework; computerized tools; density; design; genetic manipulation; in vivo; interdisciplinary approach; knock-down; mutant; research study; scoliosis; two-photon

 DESCRIPTION: The proposed research pioneers the study of the dynamic interrelationship between in vivo heterogeneous individual cell behavior and systems-level tissue properties. The project employs multiplex in vivo single cell imaging and computational analyses of tailbud cell motion to elucidate the mechanical basis of both normal vertebrate body elongation and structural musculoskeletal defects such as scoliosis. A central hypothesis of this proposal is that key systems properties of developing tissues, such as the correlation length of cell motion and cell packing, are under genetic regulation to enable robust control of symmetry maintenance and symmetry breaking. To uncover the general design principles of such regulation, the team will combine zebrafish genetics and live imaging with single cell resolution with analytical and computational tools from fluid mechanics and soft matter physics. Using this interdisciplinary approach, the team will create a 4D computational model (3D with time evolution) of the extending zebrafish tailbud incorporating cell-cell interactions, cell motion, cell packing and dynamic tissue boundaries. By comparing and contrasting the wild-type cell flow and contorted phenotypes, the team will produce a better understanding of the physical parameters that must be genetically regulated for linear body elongation. In other words, the experimental and computational systems analysis of cell motion will integrate genetics and multi-scale mechanics (i.e. molecular, cell and tissue level) into a unified ontogeny of abnormal curvatures of the spina column.

 描述：这项拟议的研究开创了体内异质个体细胞行为和系统级组织属性之间动态相互关系的研究。该项目采用体内多路单细胞成像和尾芽细胞运动的计算分析，以阐明正常脊椎动物身体伸长和脊柱侧弯等结构性肌肉骨骼缺陷的力学基础。这一提议的一个中心假设是 发育中组织的关键系统属性，如细胞运动和细胞堆积的相关长度，受到基因调控，以实现对对称性保持和对称性破坏的强大控制。为了揭示这种规则的一般设计原则，该团队将把斑马鱼遗传学和具有单细胞分辨率的活体成像与流体力学和软物质物理的分析和计算工具结合起来。使用这种跨学科的方法，该团队将创建一个4D计算模型(3D随时间演变)，其中包括细胞-细胞相互作用、细胞运动、细胞堆积和动态组织边界。通过比较和对比野生型细胞流和扭曲的表型，该团队将更好地理解线性身体伸长必须受到基因调控的物理参数。换句话说，细胞运动的实验和计算系统分析将把遗传学和多尺度力学(即分子、细胞和组织水平)整合到脊柱异常弯曲的统一个体发生学中。