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.

项目总结 塑造复杂的形态人体平面图需要生物物理和 控制单个细胞和群体所需的广泛行为的生化线索 细胞的数量。细胞水平上的生物机械力影响细胞皮质的功能：血浆 细胞膜及其下面的皮质细胞骨架。这些机械信号必须被细胞感知到， 然后采取适当的行动，如果不这样做，就会导致不正常的发展。因此，细胞 机械调节具有基本的发育和细胞生物学意义以及重要的临床意义。 关联性。这项提案的总体目标是描述机械调节的贡献。 正常发育所需的细胞功能信号及其错误调控的后果 导致细胞功能异常和/或发育障碍。果蝇提供了一种极好的， 基因顺从的，研究这些基本过程的模型 动态活体成像的可获得性和最先进的发育/细胞/分子 可用的技术和试剂。我们的长期目标是了解机械线索是如何 在胚胎发育过程中，细胞感知并作用于它们以指导它们的功能。为此，我们 建议使用细胞损伤产生的力作为诱导系统，在其中研究 细胞皮质的力学特性，包括膜张力、皮质细胞骨架动力学 以及这些属性的整合。这项建议的具体目的是：1)确定 胚胎皮质中参与张力调节的支架的性质，以及2)为了阐明 调节肌动球蛋白组织的机制，这是产生收缩力量所必需的 细胞。在这些研究中收集的信息将提供对机械的新见解 细胞的特征，以及更好地理解细胞如何解释 作用于它的内在和外在力量，以协调复杂的功能和相互作用。