Compaction is the first morphogenetic movement of the eutherian mammals and involves a developmentally regulated adhesion process. Previous studies investigated cellular and mechanical aspects of compaction. During mouse and human compaction, cells spread onto each other as a result of a contractility-mediated increase in surface tension pulling at the edges of their cell-cell contacts. However, how compaction may affect the mechanical stability of cell-cell contacts remains unknown. Here, we used a dual pipette aspiration assay on cell doublets to quantitatively analyze the mechanical stability of compacting mouse embryos. We measured increased mechanical stability of contacts with rupture forces growing from 40 to 70 nN, which was highly correlated with cell-cell contact expansion. Analyzing the dynamic molecular reorganization of cell-cell contacts, we find minimal recruitment of the cell-cell adhesion molecule Cdh1 (also known as E-cadherin) to contacts but we observe its reorganization into a peripheral adhesive ring. However, this reorganization is not associated with increased effective bond density, contrary to previous reports in other adhesive systems. Using genetics, we reduce the levels of Cdh1 or replace it with a chimeric adhesion molecule composed of the extracellular domain of Cdh1 and the intracellular domain of Cdh2 (also known as N-cadherin). We find that reducing the levels of Cdh1 impairs the mechanical stability of cell-cell contacts due to reduced contact growth, which nevertheless show higher effective bond density than wild-type contacts of similar size. On the other hand, chimeric adhesion molecules cannot form large or strong contacts indicating that the intracellular domain of Cdh2 is unable to reorganize contacts and/or is mechanically weaker than the one of Cdh1 in mouse embryos. Together, we find that mouse embryo compaction mechanically strengthens cell-cell adhesion via the expansion of Cdh1 adhesive rings that maintain pre-compaction levels of effective bond density.

中文翻译：

---

小鼠胚胎压缩过程中细胞间粘附的机械强化

压缩是真兽类哺乳动物的第一个形态发生运动，涉及发育调节的粘附过程。先前的研究调查了压实的细胞和机械方面。在小鼠和人类的压缩过程中，细胞由于收缩性介导的表面张力增加而相互扩散，拉扯细胞与细胞接触的边缘。然而，压实如何影响电池-电池接触的机械稳定性仍然未知。在这里，我们对细胞双联体使用双吸管抽吸测定来定量分析压缩小鼠胚胎的机械稳定性。我们测量到断裂力从 40 nN 增长到 70 nN 时接触的机械稳定性增加，这与细胞间接触扩张高度相关。分析细胞-细胞接触的动态分子重组，我们发现细胞-细胞粘附分子 Cdh1（也称为 E-钙粘蛋白）向接触的招募最少，但我们观察到它重组为外围粘附环。然而，与其他粘合剂系统的先前报道相反，这种重组与有效粘合密度的增加无关。利用遗传学，我们降低了 Cdh1 的水平或用由 Cdh1 胞外结构域和 Cdh2 胞内结构域（也称为 N-钙粘蛋白）组成的嵌合粘附分子取代它。我们发现，降低 Cdh1 的水平会由于接触生长减少而损害细胞-细胞接触的机械稳定性，但与相似尺寸的野生型接触相比，其显示出更高的有效键密度。另一方面，嵌合粘附分子不能形成大的或强的接触，这表明 Cdh2 的胞内结构域不能重组接触和/或在机械上比小鼠胚胎中的 Cdh1 的胞内结构域弱。我们共同发现，小鼠胚胎压实通过 Cdh1 粘合环的扩张以机械方式增强细胞与细胞的粘附，从而维持预压实水平的有效粘合密度。