A Computational Study of the Development of Epithelial Acini: I. Sufficient Conditions for the Formation of a Hollow Structure
- 200 Downloads
Normal hollow epithelial acini are 3-dimensional culture structures that resemble the architecture and functions of normal breast glands and lobules. This experimental model enables in vitro investigations of genotypic and molecular abnormalities associated with epithelial cancers. However, the way in which the acinar structure is formed is not yet completely understood. Gaining more information about consecutive stages of acini development—starting from a single cell that gives rise to a cluster of randomly oriented cells, followed by cell differentiation that leads to a layer of polarised cells enclosing the hollow lumen—will provide insight into the transformations of eukaryotic cells that are necessary for their successful arrangement into an epithelium. In this paper, we introduce a two-dimensional single-cell-based model representing the cross section of a typical acinus. Using this model, we investigate mechanisms that lead to the unpolarised cell growth, cell polarisation, stabilisation of the acinar structure and maintenance of the hollow lumen and discuss the sufficient conditions for each stage of acinar formation. In the follow-up paper (Rejniak and Anderson, A computational study of the development of epithelial acini. II. Necessary conditions for structure and lumen stability), we investigate what morphological changes are observable in the growing acini when some assumptions of this model are relaxed.
KeywordsDevelopment of epithelial acini Cell polarisation Cell apoptosis Single-cell-based model Immersed boundary method
Unable to display preview. Download preview PDF.
- Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., Walter, P., 2002. Molecular biology of the cell. Garland Science, 4th edn. Google Scholar
- Ardens, M.J., Wyllie, A.H., 1991. Apoptosis: mechanisms and roles in pathology. Int. Rev. Exp. Pathol. 32, 223–254. Google Scholar
- Bowen, I.D., Lockshin, R.A., 1981. Cell Death in Biology and Pathology. Kluwer Academic, Dordercht. Google Scholar
- Ferguson, D.J.P., Anderson, T.J., 1981. Ultrastructural observations on cell death by apoptosis in the “resting” human breast. Virchows Arch. Pathol. Anat. 393, 193–203. Google Scholar
- Laurent, V.M., Planus, E., Fodil, R., Isabey, D., 2003. Mechanical assessment by magnetocytometry of the cytosolic and cortical cytoskeletal compartments in adherent epithelial cells. Biorheology 40, 235–240. Google Scholar
- Rejniak, K.A., 2002. A computational model of the mechanics of growth of a trophoblast tissue. PhD thesis, Tulane University. Google Scholar
- Rejniak, K.A., 2007b. Modelling the development of complex tissues using individual viscoelastic cells. In: A.R.A. Anderson, M.A.J. Chaplain, K.A. Rejniak (Eds.), Single Cell Based Models in Biology and Medicine. Birkhäuser, Basel Google Scholar
- Rejniak, K.A., Anderson, A.R.A., 2007. A computational study of the development of epithelial acini. II. Necessary conditions for structure and lumen stability, in preparation. Google Scholar
- Wang, A.Z., Ojakian, G.K., Nelson, W.J., 1990a. Steps in the morphogenesis of a polarised epithelium I. Uncoupling the roles of cell–cell and cell-substratum contact in establishing plasma membrane polarity in multicellular epithelial (MDCK) cysts. J. Cell Sci. 95, 137–151. Google Scholar
- Wang, A.Z., Ojakian, G.K., Nelson, W.J., 1990b. Steps in the morphogenesis of a polarised epithelium II. Disassembly and assembly of plasma membrane domains during reversal of epithelial cell polarity in multicellular epithelial (MDCK) cysts. J. Cell Sci. 95, 153–165. Google Scholar