Epithelial cells can assemble into cohesive monolayers with rich morphologies on substrates due to competition between elastic, edge, and interfacial effects. Here we present a molecularly based thermodynamic model, integrating monolayer and substrate elasticity, and force-mediated focal adhesion formation, to elucidate the active biochemical regulation over the cellular force landscapes in cohesive epithelial monolayers, corroborated by microscopy and immunofluorescence studies. The predicted extracellular traction and intercellular tension are both monolayer size and substrate stiffness dependent, suggestive of cross-talks between intercellular and extracellular activities. Our model sets a firm ground toward a versatile computational framework to uncover the molecular origins of morphogenesis and disease in multicellular epithelia.

由于弹性，边缘和界面效应之间的竞争，上皮细胞可在基底上组装成具有丰富形态的凝聚性单层。在这里，我们提出了一个基于分子的热力学模型，该模型整合了单层和基底的弹性以及力介导的粘着斑形成，以阐明对内聚性上皮单层细胞力态势的主动生化调节，通过显微镜和免疫荧光研究得到了证实。预测的细胞外牵引力和细胞间张力均取决于单层大小和底物刚度，提示细胞间和细胞外活性之间存在串扰。我们的模型为建立通用的计算框架奠定了坚实的基础，以揭示多细胞上皮细胞形态发生和疾病的分子起源。