Contribution of cell mechanics in promoting collective behavior for supracellular migration

细胞力学在促进超细胞迁移集体行为中的贡献

• 批准号: 10680022
• 负责人: Selena Gupta
• 金额: $ 4.77万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10680022
• 关键词: Actomyosin; Affect; Back; Behavior; Bilateral; Biochemical; Biological Phenomena; Biological Process; Cell Shape; Cells; Cellular Morphology; Characteristics; Chordata; Communication; Computer Models; Coupling; Cytoskeletal Modeling; Cytoskeleton; Development; Dorsal; Embryo; Endoderm; Epidermis; Equilibrium; Exhibits; Generations; Hydrostatic Pressure; Individual; Intercellular Junctions; Invertebrates; Maintenance; Measurement; Mechanics; Methods; Modeling; Morphogenesis; Morphology; Movement; Myosin ATPase; Neoplasm Metastasis; Relaxation; Research Proposals; Reverse engineering; Role; Shapes; Side; Speed; Structure; System; Tail; Testing; Tissues; Travel; Urochordata; Vertebrates; Work; biophysical properties; cell motility; embryo tissue; improved; in vivo; in vivo Model; in vivo imaging; kinematics; mechanical signal; migration; optogenetics; progenitor; spatiotemporal; tool; transmission process; wound healing

Project Summary Highly ordered, directed movement in collective cell migration is a result of the magnitude of coordination and communication that takes place at both the cellular and tissue level. In this proposal, we focus on understanding the mechanisms that contribute to the system behaving as a ‘collective’ to achieve such phenomenon. The cardiopharyngeal progenitors of the tunicate Ciona provide the simplest model of collective cell migration, with cohesive bilateral cell pairs polarizing and migrating between the ventral epidermis and trunk endoderm. Bernadskaya & Yue et al. 2021 found that the collective cell migration of Ciona exhibits supracellular characteristics; while each cell has the machinery to migrate individually, for successful development, the cells travel together and take on the identity of either the ‘leader’ or ‘trailer’. How this collective polarity is established and communicated between the two cells, and the type of information being exchanged, remains to be elucidated. We propose that this collective migration is driven by a “rear-engine” with supracellular polarity, as mechanical information flows from the trailer cell to the leader cell. We speculate that the cell:cell junction serves as a point of plasticity; preliminary work has shown that the junction has relatively low levels of actomyosin, allowing it to be under low tension and easily deformable. We hypothesize the two cells are utilizing cell shape – specifically the direction and degree of deformation at the cell:cell junction – and hydrostatic pressure as a method for mechanical coupling. To test our hypothesis, we will use in vivo images to reverse-engineer forces, extract force measurements, and build computational models of migration. Then, we will experimentally validate the role of the cell:cell junction as an information hub contributing to supracellular polarity, cytoskeletal organization, as well as force generation and transmission.

项目摘要 集体细胞迁移中高度有序的定向运动是协调幅度的结果 以及在细胞和组织水平上进行的通信。在此提案中，我们专注于 理解有助于系统作为“集体”实现此类的机制 现象。皮象ciona的心咽祖细胞提供了最简单的集体模型 细胞迁移，具有粘性双侧细胞对偏振和腹侧表皮和躯干之间的迁移 内胚层。 Bernadskaya＆Yue等。 2021年发现，ciona的集体细胞迁移表现出上细胞上的 特征;虽然每个单元都有可以单独迁移的机器，但要成功开发，但细胞 一起旅行，并承担“领导者”或“拖车”的身份。如何建立这种集体极性 并在两个单元格之间进行通信，以及交换的信息类型，仍然是 阐明。我们建议这种集体迁移是由具有细胞上极性的“后引擎”驱动的， 机械信息从拖车电池流到领导者单元。我们推测细胞：细胞连接服务 作为可塑性；初步工作表明，该连接的肌动蛋白水平相对较低， 使其处于低张力下，易于变形。我们假设两个单元格使用细胞形状 - 特别是细胞处的变形方向和程度：细胞连接 - 静水压力作为A 机械耦合的方法。为了检验我们的假设，我们将使用体内图像来反向工程力， 提取力量测量，并建立迁移的计算模型。然后，我们将通过实验验证 细胞的作用：细胞连接作为导致细胞上极性，细胞骨架的信息中心 组织以及力产生和传播。