Mechanoregulation of Cell Functions during Embryogenesis

胚胎发生过程中细胞功能的机械调节

• 批准号: 10407016
• 负责人: SUSAN M PARKHURST
• 金额: $ 35.79万
• 依托单位: FRED HUTCHINSON CANCER CENTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-20 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10407016
• 关键词: Actins; Actomyosin; Affect; Annexins; Behavior; Biochemical; Biological; Biomechanics; Biophysics; Cell membrane; Cell physiology; Cell-Cell Adhesion; Cells; Characteristics; Complement; Complex; Cues; Cytokinesis; Cytoskeletal Proteins; Cytoskeleton; Development; Developmental Cell Biology; Disease; Drosophila genus; Due Process; Embryo; Embryonic Development; Event; Failure; Foundations; Future; Generations; Genetic; Goals; Image; Individual; Learning; Mammalian Cell; Mechanical Stress; Mechanics; Membrane; Microfilaments; Mitochondria; Modeling; Molecular; Morphogenesis; Morphology; Muscular dystrophy cardiomyopathy; Nature; Neoplasm Metastasis; Pathway interactions; Process; Property; Proteins; Reagent; Regulation; Role; Route; Signal Transduction; System; Techniques; Tissues; Work; behavior influence; cell behavior; cell cortex; clinically relevant; developmental disease; experimental study; genetic approach; imaging approach; in vivo imaging; insight; interest; mechanical properties; mechanical signal; mechanotransduction; prevent; response; scaffold; tumor progression; wound; wound healing

PROJECT SUMMARY Sculpting complex morphological body plans requires the precise orchestration of biophysical and biochemical cues to control the wide range of behaviors demanded of individual cells, as well as groups of cells. Biomechanical forces at the cell level affect the functions of the cell cortex: the plasma membrane and its underlying cortical cytoskeleton. These mechanical cues must be sensed by the cell, then properly acted upon, with the failure to do so leading to abnormal development. Thus, cell mechanoregulation is of fundamental developmental and cell biology interest and significant clinical relevance. The general aim of this proposal is to delineate the contribution of mechanoregulatory signals to cell functions required for normal development, and the consequences of their mis-regulation leading to aberrant cell functions and/or developmental disorders. Drosophila provides an excellent, genetically amenable, model in which to investigate these fundamental processes due to its accessibility to dynamic in vivo imaging and the wealth of state-of-the-art developmental/cell/molecular techniques and reagents available. Our long-term goal is to understand how mechanical cues are sensed, then acted upon, by cells to guide their functions during embryogenesis. To this end, we propose to use the forces generated by cellular wounding as an inducible system in which to study the mechanical properties of the cell cortex, including membrane tension, cortical cytoskeleton dynamics and the integration of these properties. The specific aims of this proposal are: 1) to determine the nature of the scaffold at the embryo cortex involved in tension regulation, and 2) to elucidate the mechanisms regulating actomyosin organization necessary for generating contractile forces within cells. The information gathered in these studies will provide new insight into the mechanical characteristics of the cell, as well as provide a better understanding of how the cell interprets the intrinsic and extrinsic forces acting upon it to orchestrate complex functions and interactions.

项目摘要 雕刻复杂的形态体计划需要精确的生物物理和 生化线索控制单个细胞所需的广泛行为以及组 细胞。细胞水平的生物力学作用影响细胞皮质的功能：血浆 膜及其潜在的皮质细胞骨架。这些机械提示必须由细胞感知 然后正确地采取了行动，因此未能导致异常发展。因此，细胞 机械调节具有基本发育和细胞生物学的兴趣和显着的临床 关联。该提案的总体目的是描述机械调节的贡献 正常发育所需的细胞功能的信号及其错误调节的后果 导致异常细胞功能和/或发育障碍。果蝇提供了极好的 遗传上可符合的模型，在其中研究这些基本过程 可访问动态体内成像和最先进的发育/细胞/分子的财富 可用的技术和试剂。我们的长期目标是了解机械提示 在胚胎发生过程中，通过细胞感应并作用于细胞来指导其功能。为此，我们 建议将细胞伤害产生的力作为诱导系统，在其中研究 细胞皮质的机械性能，包括膜张力，皮质细胞骨架动力学 以及这些属性的集成。该提案的具体目的是：1）确定 涉及张力调节的胚胎皮质的支架的性质，2）阐明 调节肌动球蛋白组织的机制，需要在内部产生收缩力 细胞。这些研究中收集的信息将为机械提供新的见解 细胞的特征，并可以更好地理解细胞的解释 固有的和外在的力作用于它，以协调复杂的功能和相互作用。