Mechanoregulation of Cell Functions during Embryogenesis

胚胎发生过程中细胞功能的机械调节

基本信息

批准号：
10170395
负责人：
SUSAN M PARKHURST
金额：
$ 16.37万
依托单位：
FRED HUTCHINSON CANCER RESEARCH CENTER
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-20 至 2022-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10170395
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 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 Stress 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 mechanotransduction prevent response scaffold tumor progression wound wound healing

项目摘要

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.

项目概要塑造复杂的形态身体计划需要精确协调生物物理和控制单个细胞以及群体所需的广泛行为的生化线索细胞。细胞水平的生物力学力影响细胞皮质的功能：血浆膜及其底层的皮质细胞骨架。这些机械信号必须被细胞感知到，然后采取适当的行动，否则会导致发育异常。因此，细胞机械调节具有基本的发育和细胞生物学意义，并且具有重要的临床意义关联。该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节的后果导致细胞功能异常和/或发育障碍。果蝇提供了极好的、遗传上适合的模型，在其中研究这些基本过程，由于其动态体内成像的可及性和最先进的发育/细胞/分子的丰富性可用的技术和试剂。我们的长期目标是了解机械提示的作用细胞感知并采取行动，在胚胎发生过程中指导其功能。为此，我们提议使用细胞损伤产生的力作为诱导系统来研究细胞皮质的机械特性，包括膜张力、皮质细胞骨架动力学以及这些属性的整合。本提案的具体目标是： 1) 确定参与张力调节的胚胎皮质支架的性质，以及2）阐明调节肌动球蛋白组织的机制是产生收缩力所必需的细胞。这些研究中收集的信息将为机械结构提供新的见解。细胞的特征，并提供对细胞如何解释的更好的理解内在和外在的力量作用于它以协调复杂的功能和相互作用。