npj Computational Materials

Active cell-matrix coupling regulates cellular force landscapes of cohesive epithelial monolayers （活细胞-基质偶联调节粘附性上皮细胞单层的力的面貌)
Tiankai Zhao, Yao Zhang, Qiong Wei, Xuechen Shi, Peng Zhao, Long-Qing Chen & Sulin Zhang
npj Computational Materials 4:10 (2018)
doi:10.1038/s41524-018-0069-8
Published online:14 March 2018
Abstract| Full Text | PDF OPEN

摘要:上皮细胞在基底上因弹性、边缘和界面三个效应的综合作用，可以形成形态丰富的粘着单层。基于分子热力学模型、单层-基底弹性的整合和力-介导的粘着形成，本研究提出了粘着形成机制，以阐明针对粘附上皮单层细胞力状况的活跃生化调节，并借助显微观察和免疫荧光染色研究加以证实。预测结果表明，细胞外牵引力和细胞间张力均为细胞单层尺寸依赖性和基质刚度依赖性，提示细胞内、外分子运动之间存在相互信息交流。我们的模型为多用途计算框架奠定了坚实的基础，可用来揭示多细胞上皮形态发生和疾病的分子起源。　　

Abstract: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.

Editorial Summary

Mechanobiology: Division of forces across a cell monolayer （力生物学：细胞单层上力的分解)

细胞通过粘着斑感受其外环境，可将其想象为机械连接。虽然力生物学研究主要集中于单个细胞，但来自美国宾州大学Sulin Zhang教授等，探索了多细胞作为整体如何传递和分配牵引力。作者建立了一个热力学模型，并通过显微观察牵引力作用等实验测量方法来验证该模型的预测结果。他们发现，在单层边缘，粘着斑通过与细胞外基质的相互作用产生强大牵引力，而在细胞单层中心的细胞应激水平得到提升的同时仅遭受到较低牵引力。该模型将有助于解释局部环境如何影响细胞决策，也将促进上皮组织中诸如形态发生或集体迁移等更为复杂问题的研究。

Cells sense their extracellular environment using focal adhesions, which can be imagined as mechanical linkages. While mechanobiological research mostly focuses on single cells, a team led by Sulin Zhang at Pennsylvania State University explored how multicellular ensembles transmit and distribute traction forces. The authors develop a thermodynamic model and validate predictions by experimental measures including traction force microscopy.They find that at the monolayer outline focal adhesions generate high traction force through interaction with the extracellular substrate, whereas cells in the centre of the sheet experience low traction force but have elevated cellular stress levels. This model will help to decipher how the local environment influences cellular decisions and will spur research on more complex problems of epithelial tissues, such as morphogenesis or collective migration.