Epithelial cells form continuous sheets of cells that exist in tensional homeostasis. Homeostasis is maintained through cell-to-cell junctions that distribute tension and balance forces between cells and their underlying matrix. Disruption of tensional homeostasis can lead to epithelial–mesenchymal transition (EMT), a transdifferentiation process in which epithelial cells adopt a mesenchymal phenotype, losing cell–cell adhesion and enhancing cellular motility. This process is critical during embryogenesis and wound healing, but is also dysregulated in many disease states. To further understand the role of intercellular tension in spatial patterning of epithelial cell monolayers, we developed a multicellular computational model of cell–cell and cell–substrate forces. This work builds on a hybrid cellular Potts model (CPM)–finite element model to evaluate cell–matrix mechanical feedback of an adherent multicellular cluster. Cellular movement is governed by thermodynamic constraints from cell volume, cell–cell and cell–matrix contacts, and durotaxis, which arises from cell-generated traction forces on a finite element substrate. Junction forces at cell–cell contacts balance these traction forces, thereby producing a mechanically stable epithelial monolayer. Simulations were compared to in vitro experiments using fluorescence-based junction force sensors in clusters of cells undergoing EMT. Results indicate that the multicellular CPM model can reproduce many aspects of EMT, including epithelial monolayer formation dynamics, changes in cell geometry, and spatial patterning of cell–cell forces in an epithelial tissue.

上皮细胞形成连续的细胞片，存在于张力稳态中。体内平衡是通过细胞与细胞的连接来维持的，这种连接在细胞及其底层基质之间分配张力和平衡力。张力稳态的破坏可导致上皮-间质转化（EMT），这是一种转分化过程，其中上皮细胞采用间质表型，失去细胞间粘附并增强细胞运动性。这一过程在胚胎发生和伤口愈合过程中至关重要，但在许多疾病状态下也失调。为了进一步了解细胞间张力在上皮细胞单层空间图案中的作用，我们开发了细胞-细胞和细胞-基质力的多细胞计算模型。这项工作建立在混合细胞 Potts 模型 (CPM) 和有限元模型的基础上，用于评估粘附多细胞簇的细胞 - 基质机械反馈。细胞运动受到细胞体积、细胞与细胞和细胞与基质接触以及杜罗轴（由细胞在有限元基底上产生的牵引力产生）的热力学约束的控制。细胞与细胞接触处的连接力平衡这些牵引力，从而产生机械稳定的上皮单层。将模拟与在经历 EMT 的细胞簇中使用基于荧光的连接力传感器的体外实验进行比较。结果表明，多细胞 CPM 模型可以重现 EMT 的许多方面，包括上皮单层形成动力学、细胞几何形状的变化以及上皮组织中细胞间力的空间模式。