Tan Rui Zhen, Lai Tanny, Chiam K-H
Bioinformatics Institute, A*STAR, Singapore, 30 Biopolis St, #07-01 Matrix, 138671, Singapore.
Phys Biol. 2017 Jul 19;14(4):046003. doi: 10.1088/1478-3975/aa7afc.
A multilayered epithelium is made up of individual cells that are stratified in an orderly fashion, layer by layer. In such tissues, individual cells can adopt a wide range of shapes ranging from columnar to squamous. From histological images, we observe that, in flat epithelia such as the skin, the cells in the top layer are squamous while those in the middle and bottom layers are columnar, whereas in tubular epithelia, the cells in all layers are columnar. We develop a computational model to understand how individual cell shape is governed by the mechanical forces within multilayered flat and curved epithelia. We derive the energy function for an epithelial sheet of cells considering intercellular adhesive and intracellular contractile forces. We determine computationally the cell morphologies that minimize the energy function for a wide range of cellular parameters. Depending on the dominant adhesive and contractile forces, we find four dominant cell morphologies for the multilayered-layered flat sheet and three dominant cell morphologies for the two-layered curved sheet. We study the transitions between the dominant cell morphologies for the two-layered flat sheet and find both continuous and discontinuous transitions and also the presence of multistable states. Matching our computational results with histological images, we conclude that apical contractile forces from the actomyosin belt in the epithelial cells is the dominant force determining cell shape in multilayered epithelia. Our computational model can guide tissue engineers in designing artificial multilayered epithelia, in terms of figuring out the cellular parameters needed to achieve realistic epithelial morphologies.
多层上皮组织由单个细胞组成，这些细胞以有序的方式分层排列。在这样的组织中，单个细胞可以呈现从柱状到鳞状的多种形状。从组织学图像中，我们观察到，在诸如皮肤这样的扁平上皮组织中，顶层的细胞是鳞状的，而中间层和底层的细胞是柱状的；而在管状上皮组织中，所有层的细胞都是柱状的。我们开发了一个计算模型来理解多层扁平上皮组织和弯曲上皮组织内的机械力如何控制单个细胞的形状。我们考虑细胞间粘附力和细胞内收缩力，推导出细胞上皮片的能量函数。我们通过计算确定了在各种细胞参数下使能量函数最小化的细胞形态。根据主要的粘附力和收缩力，我们发现多层扁平片有四种主要的细胞形态，两层弯曲片有三种主要的细胞形态。我们研究了两层扁平片主要细胞形态之间的转变，发现了连续和不连续的转变以及多稳态的存在。将我们的计算结果与组织学图像相匹配，我们得出结论，上皮细胞中肌动球蛋白带产生的顶端收缩力是决定多层上皮组织中细胞形状的主要力量。我们的计算模型可以指导组织工程师设计人工多层上皮组织，帮助他们确定实现逼真上皮形态所需的细胞参数。
