Cancer Chaste: Developing computational models of cancer and tissue remodelling
Latest news
- July 2011: We announce a Cell-based Chaste Workshop to happen at the Department of Computer Science, University of Oxford 4-6 January 2012
- June 2011: Members of the cell based development team attended the ECMTB conference in Krakow, Poland. The conference included a minisymposium on Chaste "Multiscale modelling of biological systems: the Chaste framework".
Introduction and aims
Mathematical and computational models of biological systems are rapidly increasing in complexity. This is especially true of fields such as cancer modelling, where the amount of available biological data is increasing exponentially. Modelling approaches therefore span the range from detailed models of molecular level changes and interactions that take place in the initial stages of cancer, right through to mechanical models of the mechanics of tumour development at the tissue level.
The objective of the cancer Chaste project is to develop a mathematical and computational model that bridges across these spatial and temporal scales within a single, generic modelling framework. The focus was initially on colorectal cancer, which was chosen due to the availability of particularly good experimental data, and since its biological understanding is sufficiently advanced to allow such a systems-level approach. Colorectal cancers originate from the epithelium that covers the luminal surface of the intestinal tract. This epithelium renews itself rapidly more rapidly than any other tissue. This process of renewal requires a coordinated programme of cell proliferation, migration and differentiation, which begins in the of tiny crypts of Lieberkühn that descend from the epithelium into the underlying connective tissue. It is generally believed that carcinogenesis occurs as a consequence of changes that disrupt normal crypt dynamics. Identifying the mechanisms that govern crypt dynamics is therefore essential to understanding the origins of colorectal cancer. We have developed a multiscale model of intestinal crypt dynamics, which comprises three main components: models of intracellular signalling pathways models; cell-cycle models; and a mechanical model that controls cell adhesion and migration at the macroscale.
The cancer Chaste code has since been developed into a general framework for modelling tumour growth and tissue remodelling. To demonstrate this generality, we have developed a multiscale model of the growth of monolayers and multicellular tumour spheroids, two common in vitro experimental systems that mimic the morphology and growth of avascular tumours in vivo.
User functionality
- Simulation of both cell-centre- and vertex-based models of cell populations in one, two or three spatial dimensions.
- Ability to define different force laws for cell-cell interactions.
- Ability to define different boundary conditions and geometric domains.
- Ability to define different cell killer objects, which govern the conditions in which cells undergo necrosis/apoptosis.
- Ability to define different cell-cycle models, which govern cell proliferation and quiescence.
- Ability to define different cell proliferative types (stem, transit amplifying and differentiated cells).
- Ability to define different cell mutation states, which can effect cell proliferation, migration and adhesion.
- Ability to define reaction-diffusion equations for key nutrients or signalling molecules, whose concentrations may influence (and in turn be influenced by) any of the above.
- Visualization and post-processing of simulation results.
Example simulation results
Screenshots
Top left: Snapshot of an intestinal crypt simulation. Here the crypt is modelled on a cylindrical geometry, by performing the simulation on a plane and enforcing periodicity on the left and right edges. Transit cells are shown in yellow, differentiated cells in red, and the blue cells are the progeny of a single cell that was dyed at the beginning of the simulation. Top right: An intestinal crypt simulation in which the membrane-bound and cytoplasmic levels of the protein beta-catenin are illustrated. Bottom: Simulation of a growing multicell tumour spheroid, showing formation of a necrotic core.
Movies
In addition to the examples shown below, you can find a variety of movies of simulations using the cancer and cell-based Chaste code on the Chaste YouTube channel.Left: a crypt represented by a cell-centre model (left) and a cell-vertex model (right). Right: a crypt represented by a cell-centre model with a population of mutant cells shown in black, the simulation on the right represents mutant cells with increased adhesivenes.
Left: monoclonal conversion in a healthy crypt using a cylindrical geometry. Right: cross secional simulation of a crypt including stomal cells and basment membrane.
Left: monoclonal conversion in a healthy crypt in a three dimensional fixed geometry. Right: demo of a simulation with multiple crypts.
