Abstract
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.
Highlights
Cell theory postulates that cell is the building block of an organism
We describe applications of our cell model and simulation method to illustrate how they can be used to explore mechanisms of cellular pattern formation in nature
An example of tissue development starting from a single cell is shown in Fig 8 (S1 Movie), which can serve as a toy model for studying the early stage of embryogenesis
Summary
Cell theory postulates that cell is the building block of an organism. It assumes that the behavior of an organism is the sum of the actions of individual cells that constitute the organism (see [1] for detailed review of this once widely accepted theory). The organismal theory treats the organism as a whole, rather than looking at its individual parts, i.e. cells. Several studies have shown that mutations that affect the size or shape of individual cells can change the size and shape of the organ, as seen in plant leaf [2, 3]. It was shown that there exists cooperation between leaf cells at some level, suggesting the existence of an organismic response [1, 3, 4]. How different tissue patterns arise mechanistically is an important question. It is challenging to design and conduct studies to identify specific effects of different attributes of individual cells and cell-cell interactions on cellular pattern formation. Computational studies can complement experimental studies in providing important insight. A number of computational methods have already been developed [5,6,7,8,9,10,11,12]
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