Department of Computer Science, University of Oxford, Wolfson Building, Parks Road, Oxford, OX1 3QD, UK.
J Theor Biol. 2012 Apr 7;298:82-91. doi: 10.1016/j.jtbi.2011.12.013. Epub 2011 Dec 22.
The role of the basement membrane is vital in maintaining the integrity and structure of an epithelial layer, acting as both a mechanical support and forming the physical interface between epithelial cells and the surrounding connective tissue. The function of this membrane is explored here in the context of a growing epithelial monolayer, defined such that the epithelial cells divide and migrate along a deformable substrate. A discrete, off-lattice cell-centre modelling approach is undertaken, which permits definition of a basement membrane component, separating the epithelial cells from the tissue stroma whilst responding to forces from both that arise due to cell division, migration and apoptosis. This model is applicable to a range of biological epithelia, including the self-renewing interfollicular epidermis, the olfactory epithelium and the intestinal crypts of Lieberkühn, to inform response and recovery of such tissues following injury. Model simulations show that homeostasis of the growing monolayer can be achieved and sustained, and the necessary balance of interactive cell forces, cell migration and cell death is presented. This work is proposed as a novel extension to the body of discrete models of biological epithelia, permitting investigation of the growth and migration of epithelial cells in a deformable environment.
基膜的作用对于维持上皮层的完整性和结构至关重要,它既是机械支撑物,又是上皮细胞与周围结缔组织之间的物理界面。本研究探讨了在生长中的上皮单层的背景下,该膜的功能。这里所定义的上皮细胞是指沿着可变形基底分裂和迁移的细胞。本研究采用了离散的、非格子的细胞中心建模方法,可以定义基膜组件,将上皮细胞与组织基质分开,同时响应由细胞分裂、迁移和细胞凋亡引起的力。该模型适用于多种生物上皮组织,包括自我更新的滤泡间表皮、嗅觉上皮和 Lieberkühn 肠隐窝,以了解组织在损伤后的反应和恢复。模型模拟表明,生长中的单层的动态平衡可以实现和维持,并呈现了相互作用的细胞力、细胞迁移和细胞死亡的必要平衡。这项工作是对生物上皮离散模型的一个新的扩展,允许在可变形环境中研究上皮细胞的生长和迁移。