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 在集体细胞迁移中，高度有序的定向运动是大量协调的结果 以及发生在细胞和组织水平上的通信。在本提案中，我们重点关注 理解有助于系统作为一个“集体”行为的机制，以实现这一目标。 现象被囊玻璃海鞘的心咽祖细胞提供了最简单的集体繁殖模型， 细胞迁移，具有粘性的双侧细胞对在腹侧表皮和躯干之间极化和迁移 内胚层Bernadskaya & Yue等人2021发现，玻璃海鞘的集体细胞迁移表现出超细胞迁移， 特征;虽然每个细胞都有单独迁移的机制，但为了成功发育，细胞 一起旅行，以“领导者”或“拖车”的身份。这种集体极性是如何建立的 以及在两个小区之间进行通信，以及正在交换的信息类型，仍然有待确定。 阐明。我们认为这种集体迁移是由具有超细胞极性的“后引擎”驱动的， 机械信息从尾单元流到首单元。我们推测细胞间连接 作为可塑性的一个点;初步研究表明该连接具有相对低水平的肌动球蛋白， 使其处于低张力下并易于变形。我们假设这两个细胞利用细胞形状 - 特别是在细胞变形的方向和程度：细胞连接-和静水压力作为一个 机械耦合方法。为了验证我们的假设，我们将使用体内图像来逆向工程力， 提取力的测量值，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：细胞连接作为一个信息中心，有助于超细胞极性，细胞骨架 组织，以及力量的产生和传递。