Contribution of cell mechanics in promoting collective behavior for supracellular migration

项目摘要 在集体细胞迁移中，高度有序的定向移动是协调程度的结果 以及在细胞和组织层面上发生的交流。在这份提案中，我们重点关注 理解有助于系统作为“集体”行为以实现这一点的机制 现象。被囊状乔纳的心咽祖细胞提供了最简单的集体模型 细胞迁移，粘连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，Ciona的集体细胞迁移表现为超细胞 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，承担起‘领队’或‘拖车’的身份。这种集体极化是如何建立起来的 并在两个单元之间进行通信，以及正在交换的信息的类型仍有待于 已澄清。我们认为，这种集体迁徙是由具有超细胞极性的“后引擎”驱动的，如 机械信息从尾部单元流向前导单元。我们推测cell：cell连接服务于 作为可塑性的一个点；初步研究表明，连接处的肌动球蛋白水平相对较低， 使其处于低张力和易变形的状态。我们假设这两个细胞利用细胞形状 -具体地说，单元格的变形方向和程度：单元格交界处-以及静水压力 机械联轴器的方法。为了验证我们的假设，我们将使用活体图像对力量进行反向工程， 提取测力，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：作为信息中枢的细胞连接有助于细胞上极性、细胞骨架 组织，以及力量的产生和传递。

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.