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

基本信息

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
项目类别：
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

项目摘要

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：拟议的研究开创了对体内异质单个细胞行为与系统级组织特性之间动态相互关系的研究。该项目采用多重体内单细胞成像和尾串细胞运动的计算分析，以阐明正常脊椎动物体伸长和结构性肌肉骨骼缺陷（如脊柱侧弯）的机械基础。该提议的一个核心假设是正在发展组织的关键系统特性，例如细胞运动和细胞填料的相关长度，在遗传调节下，以实现对对称性维持和对称性破坏的强大控制。为了揭示此类调节的一般设计原理，团队将将斑马鱼遗传学和现场成像与单细胞分辨率与流体力学和软物质物理学的分析和计算工具相结合。使用这种跨学科的方法，团队将创建一个延伸斑马鱼尾巴的4D计算模型（3D随时间演化），融合了细胞细胞相互作用，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量和受控表型，该团队将更好地了解必须在遗传上调节线性身体伸长的物理参数。换句话说，细胞运动的实验和计算系统分析将整合遗传学和多尺度力学（即分子，细胞和组织水平），使脊柱柱异常曲率的统一的本体发育。