Spatiotemporal mapping of the contractile and adhesive forces sculpting early C. elegans embryos

Embryo shape is determined by individual cell mechanics, intercellular interaction strength, and geometrical constraints. Models based on surface tensions at cell interfaces can predict 3D static cellular arrangements within aggregates. However, predicting the dynamics of such arrangements is challenging due to difficulties in measuring temporal changes in tensions. Here, we characterise the spatiotemporal changes in cellular tensions shaping the early nematode embryo using AFM, live microscopy, and tension inference. Using excoriated embryos, we validate a hybrid inference pipeline that calibrates relative inferred tensions temporally using cortical myosin enrichment and absolute tensions using AFM measurements. Applied to embryos within their native shell, we infer a spatiotemporal map of absolute tensions, revealing that ABa, ABp, and EMS compaction is driven by increased tension at free surfaces, while P2’s initial exclusion is due to high tension at intercellular contacts. We uncover a direct and non-affine contribution of cadherins to cell-cell contact tension, comparable to cadherins’ indirect contribution via actomyosin regulation.This repository contains all of the microscopy raw data and the code to produce most of the figures in the associated publication: https://doi.org/10.1101/2023.03.07.531437 Please consult the "README" document for a full description of how to do this.胚胎形态由单个细胞力学特性、细胞间相互作用强度与几何约束共同决定。基于细胞界面表面张力的模型，能够预测细胞聚集体内的三维静态细胞排布。然而，由于难以精准测量张力的动态时间变化，预测此类细胞排布的动态过程仍颇具挑战。本研究借助原子力显微镜（Atomic Force Microscopy, AFM）、活细胞显微成像及张力推断技术，对塑造早期线虫胚胎的细胞张力时空变化展开了系统表征。我们通过剥除卵壳的胚胎样本，验证了一套混合推断流程：该流程可通过皮层肌球蛋白富集水平对推算得到的相对张力进行时间校准，并依托AFM实测值完成绝对张力的校准。将该流程应用于保留天然卵壳的胚胎后，我们成功推断出绝对张力的时空分布图谱，揭示出ABa、ABp与EMS细胞的致密化过程由自由表面处的张力升高所驱动，而P2细胞的初始排斥现象则源于细胞间接触位点的高张力。本研究还发现，钙粘蛋白（cadherins）对细胞间接触张力存在直接且非仿射的贡献，其效应可与钙粘蛋白通过肌动蛋白-肌球蛋白系统调控所产生的间接贡献相媲美。本仓库包含了关联论文（https://doi.org/10.1101/2023.03.07.531437）中绝大多数图表所需的显微原始数据与生成代码。如需完整的操作指南，请参阅"README"文档。