Gord Alexander, Holmes William R, Dai Xing, Nie Qing
Center for Mathematical and Computational Biology, Department of Mathematics, University of California, Irvine, CA 92617, USA Center for Complex Biological Systems, University of California, Irvine, CA 92617, USA.
Center for Complex Biological Systems, University of California, Irvine, CA 92617, USA Department of Biological Chemistry, School of Medicine, University of California, Irvine, CA 92617, USA.
J R Soc Interface. 2014 Oct 6;11(99). doi: 10.1098/rsif.2014.0631.
Skin is a complex organ tasked with, among other functions, protecting the body from the outside world. Its outermost protective layer, the epidermis, is comprised of multiple cell layers that are derived from a single-layered ectoderm during development. Using a new stochastic, multi-scale computational modelling framework, the anisotropic subcellular element method, we investigate the role of cell morphology and biophysical cell-cell interactions in the formation of this layered structure. This three-dimensional framework describes interactions between collections of hundreds to thousands of cells and (i) accounts for intracellular structure and morphology, (ii) easily incorporates complex cell-cell interactions and (iii) can be efficiently implemented on parallel architectures. We use this approach to construct a model of the developing epidermis that accounts for the internal polarity of ectodermal cells and their columnar morphology. Using this model, we show that cell detachment, which has been previously suggested to have a role in this process, leads to unpredictable, randomized stratification and that this cannot be abrogated by adjustment of cell-cell adhesion interaction strength. Polarized distribution of cell adhesion proteins, motivated by epithelial polarization, can however eliminate this detachment, and in conjunction with asymmetric cell division lead to robust and predictable development.
皮肤是一个复杂的器官，其功能之一是保护身体免受外界侵害。它最外层的保护层，即表皮，由多个细胞层组成，这些细胞层在发育过程中源自单层外胚层。我们使用一种新的随机多尺度计算建模框架——各向异性亚细胞元方法，来研究细胞形态和生物物理细胞间相互作用在这种分层结构形成中的作用。这个三维框架描述了数百到数千个细胞集合之间的相互作用，并且（i）考虑了细胞内结构和形态，（ii）容易纳入复杂的细胞间相互作用，以及（iii）可以在并行架构上高效实现。我们使用这种方法构建了一个发育中的表皮模型，该模型考虑了外胚层细胞的内部极性及其柱状形态。使用这个模型，我们表明，先前认为在此过程中起作用的细胞脱离会导致不可预测的随机分层，并且这种情况不能通过调整细胞间粘附相互作用强度来消除。然而，由上皮极化驱动的细胞粘附蛋白的极化分布可以消除这种脱离，并与不对称细胞分裂一起导致稳健且可预测的发育。
