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: 8934125
• 负责人: SCOTT A HOLLEY
• 金额: $ 40.47万
• 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/8934125
• 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 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; 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; Relative (related person); 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; 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.