Understanding and Controlling the Cellular Forces that Coordinate Epithelial Tissue Morphogenesis

了解和控制协调上皮组织形态发生的细胞力

• 批准号: 10674731
• 负责人: Christian Michael Cupo
• 金额: $ 4.77万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10674731
• 关键词: 3-Dimensional; Actomyosin; Affect; Automobile Driving; Behavior; Cell Shape; Cells; Complex; Congenital Abnormality; Cultured Cells; Cytoskeleton; Development; Developmental Cell Biology; Disease; Disseminated Malignant Neoplasm; Drosophila genus; Drosophila melanogaster; Elasticity; Embryo; Engineering; Environment; Epithelial Cells; Epithelium; Event; Generations; Goals; Health; Human; In Vitro; Intercalated Cell; Intercellular Junctions; Length; Liquid substance; Malignant Neoplasms; Measurement; Measures; Mechanics; Morphogenesis; Movement; Myosin ATPase; Nanotechnology; Nonmuscle Myosin Type IIA; Organ; Pattern; Play; Property; Regenerative Medicine; Regulation; Resolution; Role; Shapes; Solid; Stretching; Structure; System; Techniques; Testing; Tissue Engineering; Tissues; convergent extension; density; flexibility; fluidity; graphene; improved; in vivo; mechanical force; monolayer; movie; nano; nanoengineering; nanomaterials; new technology; optogenetics; prevent; reconstitution; self organization; spatiotemporal; tissue culture; tool; two-dimensional; wound healing

Project Summary / Abstract Mechanical forces generated by the cellular actomyosin cytoskeleton are largely responsible for shaping sheets of epithelial cells into tissues and organs. During these morphogenetic events, the forces produced by myosin might locally promote or resist these shape changes. Our current understanding of how the structure of a myosin network influences tissue fluidity, the propensity of a tissue to remodel and flow, is lacking. In particular, it is not well understood why some epithelial cell sheets remodel and flow like fluids, while other stretch and bend like elastic solids, or how this is regulated during specific morphogenetic events. The goal of this project is to combine nanoengineering and optogenetic techniques to measure and manipulate tissues with high spatiotemporal precision to undercover the roles of actomyosin forces in tissue fluidity and morphogenesis. I will address these challenges by (1) studying myosin networks and tissue fluidity during convergent extension in Drosophila melanogaster, (2) quantitatively analyzing the forces generated by epithelial tissue sheets in vitro on nanofabricated substrates, and (3) applying these findings to tissues grown on a nanomaterial flexible substrate in an attempt to synthetically reconstitute and study three-dimensional tissue morphogenesis. These studies will improve our understanding of the mechanisms underlying how cells collectively self-organize and how perturbations in these mechanisms can lead to disease states.

项目总结/摘要 由细胞肌动球蛋白细胞骨架产生的机械力在很大程度上负责形成片 转化为组织和器官。在这些形态发生事件中，肌球蛋白产生的力 可能局部地促进或抵制这些形状变化。我们目前对肌球蛋白结构的理解 网络影响组织流动性，组织重塑和流动的倾向缺乏。尤其不 很好地理解为什么一些上皮细胞片重塑和流动像流体，而其他拉伸和弯曲像 弹性固体，或者在特定的形态发生事件中这是如何调节的。本项目的目标是将联合收割机 纳米工程和光遗传学技术来测量和操纵具有高时空的组织 精确性来掩盖肌动球蛋白力在组织流动性和形态发生中的作用。我会解决这些问题 挑战：（1）研究果蝇会聚延伸过程中的肌球蛋白网络和组织流动性 （2）定量分析体外上皮组织片对 将这些发现应用于在纳米材料柔性基底上生长的组织 试图综合重建和研究三维组织形态发生。这些研究将 提高我们对细胞如何集体自组织的机制的理解， 这些机制的紊乱可导致疾病状态。