Developing multi-cell developmental and biomedical simulations using CompuCell3D

Prof. James A. Glazier

Biocomplexity Institute and Department of Physics

Indiana University

Swain Hall West 159

727 East Third Street

Bloomington, IN 47405-7105

e-mail: glazier@indiana.edu Phone: +1 (812) 855-3735

Abstract: The tutorial will introduce CompuCell3D – an open-source, multi-cell, multi-scale environment for biomedical simulations. CompuCell3D uses an easy-to-comprehend model description language and most users are able to develop simple CompuCell3D-based simulations after a 30 minute introductory lecture. By the end of the half-day tutorial, participants will be able to build simulations including cell growth, death, motility, differential adhesion, chemotaxis, differentiation and polarization, reaction-diffusion of extracellular chemical fields and finite-element representation of elastic and plastic ECM. As a use case we will build a CompuCell3D simulation of vascularized tumor growth.

Background: CompuCell3D is a well-supported, open-source environment for building and running multi-cell simulations based on the Cellular Potts Model (CPM, aka GGH) methodology. CompuCell3D allows users to model cell behaviors at the multi-cell level. CompuCell3D also allows linking to models at subcellular scales via BionetSolver (which runs SBML models inside each cell) and to tissue and organ level via Partial Differential Equation (PDEs) and Finite Element-like methods.

While sufficiently simple that a simulation of tens of thousands of cells runs in a reasonable time on a single-processor laptop, it is detailed enough to allow specification of cell shape-change and movement, cell properties like volume, membrane area and type and cell behaviors like adhesion, chemotaxis, polarization, growth, death and division. Its fixed lattice discretization makes it computationally simple and easy to interface with tissue-level continuum models of transport and diffusion and with subcellular models of gene regulation, metabolism and signaling.

A key feature of CompuCell3D is that users define models using a model-description language, CompuCell3D Markup Language (CC3DML), and open-source Python scripting rather than hand coding in a low-level language like C++. Consequently, CompuCell3D simulations do not require code compilation. High-level model description reduces the need for detailed knowledge of numerical analysis and programming techniques required for model development, and facilitates model validation, publication, sharing and reuse.

CompuCell3D significantly reduces the time needed to develop new simulations and because it is open-source it allows users to examine the base code and enhance, modify and improve the base code as needed.

CompuCell3D simulations address, among other topics, Age-related Macular Degeneration (AMD), evaluation of radiation-treatment strategies, gastrulation and somitogenesis, Drosophila and vertebrate eye development, limb development, bone regeneration, avascular and vascular tumor progression and biofilm growth.

Logistics: The tutorial will consist of:

1) A brief introductory presentation on CPM modeling techniques – including an overview of examples of CPM-based simulations.

2) Hands-on tutorials – simple cell sorting models, vascular network formation, cell growth, division, death, and links to subcellular models.

3) User discussion, including how to build realistic vascularized tumor growth simulations as an advanced use case for CompuCell3D.

We encourage users to bring laptops so they can conduct the exercises (For Windows and OSX we provide binary installer packages. Linux, in general, will require CompuCell3D recompilation).

Target Audience: Anyone interested in building multi-cell simulations of development, homeostasis or developmental diseases like cancer. Familiarity with a scripting language like Mathematica, Matlab or Python will be helpful, but is not required.

Further Information: For more information on CompuCell3D - downloads, manuals and tutorials, please visit www.compucell3d.org. Biocomplexity Institute organizes annual CompuCell3D training workshops - please visit our website for more information.