Abstract
BackgroundCell proliferation is a key characteristic of eukaryotic cells. During cell proliferation, cells interact with each other. In this study, we developed a cellular automata model to estimate cell–cell interactions using experimentally obtained images of cultured cells.ResultsWe used four types of cells; HeLa cells, human osteosarcoma (HOS) cells, rat mesenchymal stem cells (MSCs), and rat smooth muscle A7r5 cells. These cells were cultured and stained daily. The obtained cell images were binarized and clipped into squares containing about 104 cells. These cells showed characteristic cell proliferation patterns. The growth curves of these cells were generated from the cell proliferation images and we determined the doubling time of these cells from the growth curves. We developed a simple cellular automata system with an easily accessible graphical user interface. This system has five variable parameters, namely, initial cell number, doubling time, motility, cell–cell adhesion, and cell–cell contact inhibition (of proliferation). Within these parameters, we obtained initial cell numbers and doubling times experimentally. We set the motility at a constant value because the effect of the parameter for our simulation was restricted. Therefore, we simulated cell proliferation behavior with cell–cell adhesion and cell–cell contact inhibition as variables. By comparing growth curves and proliferation cell images, we succeeded in determining the cell–cell interaction properties of each cell. Simulated HeLa and HOS cells exhibited low cell–cell adhesion and weak cell–cell contact inhibition. Simulated MSCs exhibited high cell–cell adhesion and positive cell–cell contact inhibition. Simulated A7r5 cells exhibited low cell–cell adhesion and strong cell–cell contact inhibition. These simulated results correlated with the experimental growth curves and proliferation images.ConclusionsOur simulation approach is an easy method for evaluating the cell–cell interaction properties of cells.
Highlights
Cell proliferation is a key characteristic of eukaryotic cells
We developed a system for estimating the cell–cell interactions of cultured cells using a cellular automata model
To estimate the interaction parameters, we focused on images of cells in 2 dimensional (2D) cell culture because cell–cell interactions, especially cell–cell adhesion and cell–cell contact inhibition, affect the formation of cell aggregates
Summary
Cell proliferation is a key characteristic of eukaryotic cells. During cell proliferation, cells interact with each other. We can culture many types of cells including triploblastic, stem, and cancer cells. These cells can be viable and can proliferate under 2 dimensional (2D) cell culture conditions. Cell culture is often used in cell assay systems, such as in evaluating the effect of drugs on cancer cells [2, 3]. The homotypic intercellular adhesive forces between ectoderm, mesoderm, and endoderm cells are different in each other [16] These cell–cell interactions are important properties of cells, they are hard to evaluate in standard cell assay systems. Simple methods for evaluating cell–cell interaction properties are required for the development of cell assay systems for drug screening
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