Modeling active cell movement with the Potts model

In the last decade, the cellular Potts model has been extensively used to model interacting cell systems at the tissue-level. However, in early applications of this model, cell movement was taken as a consequence of membrane fluctuations due to cell-cell interactions, or as a response to an external chemotactic gradient. Recent findings have shown that eukaryotic cells can exhibit persistent displacements across scales larger than cell size, even in the absence of external signals. Persistent cell motion has been incorporated to the cellular Potts model by many authors in the context of collective motion, chemotaxis and morphogenesis. In this paper, we use the cellular Potts model in combination with a random field applied over each cell. This field promotes a uniform cell motion in a given direction during a certain time interval, after which the movement direction changes. The dynamics of the direction is coupled to a first order autoregressive process. We investigated statistical properties, such as the mean-squared displacement and spatio-temporal correlations, associated to these self-propelled in silico cells in different conditions. The proposed model emulates many properties observed in different experimental setups. By studying low and high density cultures, we find that cell-cell interactions decrease the effective persistent time.Instituto de Investigaciones Fisicoquímicas Teóricas y AplicadasCentro Regional de Estudios Genómico

Diffusion-Limited Growth of Microbial Colonies.

The emergence of diffusion-limited growth (DLG) within a microbial colony on a solid substrate is studied using a combination of mathematical modelling and experiments. Using an agent-based model of the interaction between microbial cells and a diffusing nutrient, it is shown that growth directed towards a nutrient source may be used as an indicator that DLG is influencing the colony morphology. A continuous reaction-diffusion model for microbial growth is employed to identify the parameter regime in which DLG is expected to arise. Comparisons between the model and experimental data are used to argue that the bacterium Bacillus subtilis can undergo DLG, while the yeast Saccharomyces cerevisiae cannot, and thus the non-uniform growth exhibited by this yeast must be caused by the pseudohyphal growth mode rather than limited nutrient availability. Experiments testing directly for DLG features in yeast colonies are used to confirm this hypothesis

Cooperation and competition in the dynamics of tissue architecture during homeostasis and tumorigenesis

The construction of a network of cell-to-cell contacts makes it possible to characterize the patterns and spatial organisation of tissues. Such networks are highly dynamic, depending on the changes of the tissue architecture caused by cell division, death and migration. Local competitive and cooperative cell-to-cell interactions influence the choices cells make. We review the literature on quantitative data of epithelial tissue topology and present a dynamical network model that can be used to explore the evolutionary dynamics of a two dimensional tissue architecture with arbitrary cell-to-cell interactions. In particular, we show that various forms of experimentally observed types of interactions can be modelled using game theory. We discuss a model of cooperative and non-cooperative cell-to-cell communication that can capture the interplay between cellular competition and tissue dynamics. We conclude with an outlook on the possible uses of this approach in modelling tumorigenesis and tissue homeostasis.Comment: 11 pages, 5 figures; Seminars in Cancer Biology (2013

Implementing vertex dynamics models of cell populations in biology within a consistent computational framework

The dynamic behaviour of epithelial cell sheets plays a central role during development, growth, disease and wound healing. These processes occur as a result of cell adhesion, migration, division, differentiation and death, and involve multiple processes acting at the cellular and molecular level. Computational models offer a useful means by which to investigate and test hypotheses about these processes, and have played a key role in the study of cell–cell interactions. However, the necessarily complex nature of such models means that it is difficult to make accurate comparison between different models, since it is often impossible to distinguish between differences in behaviour that are due to the underlying model assumptions, and those due to differences in the in silico implementation of the model. In this work, an approach is described for the implementation of vertex dynamics models, a discrete approach that represents each cell by a polygon (or polyhedron) whose vertices may move in response to forces. The implementation is undertaken in a consistent manner within a single open source computational framework, Chaste, which comprises fully tested, industrial-grade software that has been developed using an agile approach. This framework allows one to easily change assumptions regarding force generation and cell rearrangement processes within these models. The versatility and generality of this framework is illustrated using a number of biological examples. In each case we provide full details of all technical aspects of our model implementations, and in some cases provide extensions to make the models more generally applicable

Modeling Active Cell Movement With the Potts Model

In the last decade, the cellular Potts model has been extensively used to model interacting cell systems at the tissue-level. However, in early applications of this model, cell movement was taken as a consequence of membrane fluctuations due to cell-cell interactions, or as a response to an external chemotactic gradient. Recent findings have shown that eukaryotic cells can exhibit persistent displacements across scales larger than cell size, even in the absence of external signals. Persistent cell motion has been incorporated to the cellular Potts model by many authors in the context of collective motion, chemotaxis and morphogenesis. In this paper, we use the cellular Potts model in combination with a random field applied over each cell. This field promotes a uniform cell motion in a given direction during a certain time interval, after which the movement direction changes. The dynamics of the direction is coupled to a first order autoregressive process. We investigated statistical properties, such as the mean-squared displacement and spatio-temporal correlations, associated to these self-propelled in silico cells in different conditions. The proposed model emulates many properties observed in different experimental setups. By studying low and high density cultures, we find that cell-cell interactions decrease the effective persistent time

Comparing individual-based approaches to modelling the self-organization of multicellular tissues.

The coordinated behaviour of populations of cells plays a central role in tissue growth and renewal. Cells react to their microenvironment by modulating processes such as movement, growth and proliferation, and signalling. Alongside experimental studies, computational models offer a useful means by which to investigate these processes. To this end a variety of cell-based modelling approaches have been developed, ranging from lattice-based cellular automata to lattice-free models that treat cells as point-like particles or extended shapes. However, it remains unclear how these approaches compare when applied to the same biological problem, and what differences in behaviour are due to different model assumptions and abstractions. Here, we exploit the availability of an implementation of five popular cell-based modelling approaches within a consistent computational framework, Chaste (http://www.cs.ox.ac.uk/chaste). This framework allows one to easily change constitutive assumptions within these models. In each case we provide full details of all technical aspects of our model implementations. We compare model implementations using four case studies, chosen to reflect the key cellular processes of proliferation, adhesion, and short- and long-range signalling. These case studies demonstrate the applicability of each model and provide a guide for model usage