论文标题
弯曲底物上上皮细胞的3D形状
3D shape of epithelial cells on curved substrates
论文作者
论文摘要
人们普遍认识到,上皮细胞的形状取决于肌动蛋白皮质产生的张力以及细胞对底物和彼此之间的粘附。为了说明这些生物学和结构对细胞形状的贡献,已经提出了不同的物理模型。但是,尚未提出一种实验程序,该程序尚未提出验证3D中上皮细胞形状的最小物理模型。在这项研究中,我们在具有正弦曲线的底物上培养了MDCK上皮细胞,从而使我们能够在各种阳性和负曲率上测量细胞的形状。我们发现,山谷中的MDCK细胞比正弦底物的冠层厚。曲率对仅使用差分顶端,基底和侧面能的模型无法理解曲率对上皮细胞形状的影响。但是,根尖线张力的添加足以定量考虑实验测量值。该模型还解释了过表达E-钙粘蛋白的MDCK细胞的形状。另一方面,当用玻利比生汀减少肌球蛋白II活性时,我们测量了山谷和波峰之间细胞厚度差异的饱和度,这表明需要限制较大细胞变形的任期。我们的结果表明,一个说明上皮细胞形状的最小模型除了差分表面能外还需要包括顶线张力,突出了在上皮细胞中产生各向异性张力的结构的重要性,例如肌动蛋白带连接粘附器连接的肌动蛋白带。将来,我们的实验过程可用于测试弯曲环境中上皮形状的更广泛的物理模型,包括连续模型。
It is widely recognized that the shape of epithelial cells is determined by the tension generated by the actomyosin cortex and the adhesion of cells to the substrate and to each other. To account for these biological and structural contributions to cell shape, different physical models have been proposed. However, an experimental procedure that would allow a validation of a minimal physical model for the shape of epithelial cells in 3D has not yet been proposed. In this study, we cultured MDCK epithelial cells on substrates with a sinusoidal profile, allowing us to measure the shape of the cells on various positive and negative curvatures. We found that MDCK cells are thicker in the valleys than on the crests of sinusoidal substrates. The influence of curvature on the shape of epithelial cells could not be understood with a model using only differential apical, basal and lateral surface energies. However, the addition of an apical line tension was sufficient to quantitatively account for the experimental measurements. The model also accounts for the shape of MDCK cells that overexpress E-cadherin. On the other hand, when reducing myosin II activity with blebbistatin, we measured a saturation of the difference in cell thickness between valleys and crests, suggesting the need for a term limiting large cell deformations. Our results show that a minimal model that accounts for epithelial cell shape needs to include an apical line tension in addition to differential surface energies, highlighting the importance of structures that produce anisotropic tension in epithelial cells, such as the actin belt linking adherens junctions. In the future, our experimental procedure could be used to test a wider range of physical models for the shape of epithelia in curved environments, including, for example, continuous models.