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Computational analysis of three-dimensional epithelial morphogenesis using vertex models.

ABSTRACT: The folding of epithelial sheets, accompanied by cell shape changes and rearrangements, gives rise to three-dimensional structures during development. Recently, some aspects of epithelial morphogenesis have been modeled using vertex models, in which each cell is approximated by a polygon; however, these models have been largely confined to two dimensions. Here, we describe an adaptation of these models in which the classical two-dimensional vertex model is embedded in three dimensions. This modification allows for the construction of complex three-dimensional shapes from simple sheets of cells. We describe algorithmic, computational, and biophysical aspects of our model, with the view that it may be useful for formulating and testing hypotheses regarding the mechanical forces underlying a wide range of morphogenetic processes.

SUBMITTER: Du X

PROVIDER: S-EPMC4256082 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Computational analysis of three-dimensional epithelial morphogenesis using vertex models.

Du XinXin X Osterfield Miriam M Shvartsman Stanislav Y SY

Physical biology 20141120 6

The folding of epithelial sheets, accompanied by cell shape changes and rearrangements, gives rise to three-dimensional structures during development. Recently, some aspects of epithelial morphogenesis have been modeled using vertex models, in which each cell is approximated by a polygon; however, these models have been largely confined to two dimensions. Here, we describe an adaptation of these models in which the classical two-dimensional vertex model is embedded in three dimensions. This modi ...[more]

PMID: 25410646

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Project description:BACKGROUND: Lungs develop from the fetal digestive tract where epithelium invades the vascular rich stroma in a process called branching morphogenesis. In organogenesis, endothelial cells have been shown to be important for morphogenesis and the maintenance of organ structure. The aim of this study was to recapitulate human lung morphogenesis in vitro by establishing a three dimensional (3D) co-culture model where lung epithelial cells were cultured in endothelial-rich stroma. METHODS: We used a human bronchial epithelial cell line (VA10) recently developed in our laboratory. This cell line cell line maintains a predominant basal cell phenotype, expressing p63 and other basal markers such as cytokeratin-5 and -14. Here, we cultured VA10 with human umbilical vein endothelial cells (HUVECs), to mimic the close interaction between these cell types during lung development. Morphogenesis and differentiation was monitored by phase contrast microscopy, immunostainings and confocal imaging. RESULTS: We found that in co-culture with endothelial cells, the VA10 cells generated bronchioalveolar like structures, suggesting that lung epithelial branching is facilitated by the presence of endothelial cells. The VA10 derived epithelial structures display various complex patterns of branching and show partial alveolar type-II differentiation with pro-Surfactant-C expression. The epithelial origin of the branching VA10 colonies was confirmed by immunostaining. These bronchioalveolar-like structures were polarized with respect to integrin expression at the cell-matrix interface. The endothelial-induced branching was mediated by soluble factors. Furthermore, fibroblast growth factor receptor-2 (FGFR-2) and sprouty-2 were expressed at the growing tips of the branching structures and the branching was inhibited by the FGFR-small molecule inhibitor SU5402. DISCUSSION: In this study we show that a human lung epithelial cell line can be induced by endothelial cells to form branching bronchioalveolar-like structures in 3-D culture. This novel model of human airway morphogenesis can be used to study critical events in human lung development and suggests a supportive role for the endothelium in promoting branching of airway epithelium.

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Computational analysis of three-dimensional epithelial morphogenesis using vertex models.

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Computational analysis of three-dimensional epithelial morphogenesis using vertex models.

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