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：所提出的研究开创了体内异质个体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芽细胞运动的计算分析来阐明两种正常的机械基础。脊椎动物身体伸长和结构性肌肉骨骼缺陷，例如脊柱侧凸，该提案的一个中心假设是组织的关键系统特性，例如细胞运动和细胞堆积的相关长度，都受到基因调控，以实现对对称性维持和对称性破坏的稳健控制。为了揭示这种调控的一般设计原理，该团队将结合斑马鱼的发育遗传学。利用流体力学和软物质物理学的分析和计算工具进行单细胞分辨率的实时成像，该团队将利用这种跨学科方法，创建一个结合细胞与细胞相互作用的斑马鱼尾芽的 4D 计算模型（随时间演化的 3D）。细胞运动，通过比较和对比野生型细胞流和扭曲的表型，研究小组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，即实验和计算。细胞运动的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育中。