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.

项目概要 集体细胞迁移中高度有序、定向的运动是协调程度的结果 在本提案中，我们重点关注发生在细胞和组织水平上的通信。 了解有助于系统作为一个“集体”表现以实现这一目标的机制 被囊动物的心咽祖细胞提供了最简单的集体模型。 细胞迁移，粘性双侧细胞对在腹侧表皮和躯干之间极化和迁移 Bernadskaya & Yue et al. 2021 发现 Ciona 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 一起旅行并承担“领导者”或“拖车者”的身份如何建立这种集体极性。 两个单元之间的通信以及交换的信息类型仍有待确定 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。 机械信息从尾部细胞流向前导细胞，我们推测细胞：细胞连接处起作用。 作为可塑性的一个点，初步工作表明连接处的肌动球蛋白水平相对较低， 使其在低张力下且易于变形，我们追求这两个单元都利用单元形状。 – 特别是细胞：细胞连接处的变形方向和程度 – 以及静水压力 为了检验我们的假设，我们将使用体内图像对力进行逆向工程， 提取力测量值并建立迁移计算模型然后，我们将通过实验进行验证。 细胞：细胞连接作为信息中心的作用，有助于细胞上极性、细胞骨架 组织，以及力量的产生和传输。