Kachalo Sëma, Naveed Hammad, Cao Youfang, Zhao Jieling, Liang Jie
Department of Bioengineering, The University of Illinois at Chicago, Chicago, IL, 60607.
Department of Bioengineering, The University of Illinois at Chicago, Chicago, IL, 60607; Computer, Electrical and Mathematical Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal, Saudi Arabia.
PLoS One. 2015 May 14;10(5):e0126484. doi: 10.1371/journal.pone.0126484. eCollection 2015.
Geometric and mechanical properties of individual cells and interactions among neighboring cells are the basis of formation of tissue patterns. Understanding the complex interplay of cells is essential for gaining insight into embryogenesis, tissue development, and other emerging behavior. Here we describe a cell model and an efficient geometric algorithm for studying the dynamic process of tissue formation in 2D (e.g. epithelial tissues). Our approach improves upon previous methods by incorporating properties of individual cells as well as detailed description of the dynamic growth process, with all topological changes accounted for. Cell size, shape, and division plane orientation are modeled realistically. In addition, cell birth, cell growth, cell shrinkage, cell death, cell division, cell collision, and cell rearrangements are now fully accounted for. Different models of cell-cell interactions, such as lateral inhibition during the process of growth, can be studied in detail. Cellular pattern formation for monolayered tissues from arbitrary initial conditions, including that of a single cell, can also be studied in detail. Computational efficiency is achieved through the employment of a special data structure that ensures access to neighboring cells in constant time, without additional space requirement. We have successfully generated tissues consisting of more than 20,000 cells starting from 2 cells within 1 hour. We show that our model can be used to study embryogenesis, tissue fusion, and cell apoptosis. We give detailed study of the classical developmental process of bristle formation on the epidermis of D. melanogaster and the fundamental problem of homeostatic size control in epithelial tissues. Simulation results reveal significant roles of solubility of secreted factors in both the bristle formation and the homeostatic control of tissue size. Our method can be used to study broad problems in monolayered tissue formation. Our software is publicly available.
单个细胞的几何和力学特性以及相邻细胞之间的相互作用是组织模式形成的基础。理解细胞间复杂的相互作用对于深入了解胚胎发育、组织发育及其他新出现的行为至关重要。在此，我们描述一种细胞模型和一种高效的几何算法，用于研究二维（如上皮组织）中组织形成的动态过程。我们的方法通过纳入单个细胞的特性以及对动态生长过程的详细描述改进了先前的方法，同时考虑了所有拓扑变化。细胞大小、形状和分裂平面方向都得到了真实的建模。此外，现在还全面考虑了细胞出生、细胞生长、细胞收缩、细胞死亡、细胞分裂、细胞碰撞和细胞重排。可以详细研究不同的细胞 - 细胞相互作用模型，例如生长过程中的侧向抑制。从任意初始条件（包括单个细胞的初始条件）开始的单层组织的细胞模式形成也可以详细研究。通过采用一种特殊的数据结构实现了计算效率，该数据结构确保在固定时间内访问相邻细胞，且无需额外的空间要求。我们已成功在1小时内从2个细胞生成了由超过20,000个细胞组成的组织。我们表明我们的模型可用于研究胚胎发育、组织融合和细胞凋亡。我们详细研究了黑腹果蝇表皮上刚毛形成的经典发育过程以及上皮组织中稳态大小控制的基本问题。模拟结果揭示了分泌因子的溶解性在刚毛形成和组织大小的稳态控制中的重要作用。我们的方法可用于研究单层组织形成中的广泛问题。我们的软件可公开获取。
