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Large-Scale Parameter Studies of Cell-Based Models of Tissue Morphogenesis Using CompuCell3D or VirtualLeaf

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Book cover Tissue Morphogenesis

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1189))

Abstract

Computational, cell-based models, such as the cellular Potts model (CPM), have become a widely used tool to study tissue formation. Most cell-based models mimic the physical properties of cells and their dynamic behavior, and generate images of the tissue that the cells form due to their collective behavior. Due to these intuitive parameters and output, cell-based models are often evaluated visually and the parameters are fine-tuned by hand. To get better insight into how in a cell-based model the microscopic scale (e.g., cell behavior, secreted molecular signals, and cell-ECM interactions) determines the macroscopic scale, we need to generate morphospaces and perform parameter sweeps, involving large numbers of individual simulations. This chapter describes a protocol and presents a set of scripts for automatically setting up, running, and evaluating large-scale parameter sweeps of cell-based models. We demonstrate the use of the protocol using a recent cellular Potts model of blood vessel formation model implemented in CompuCell3D. We show the versatility of the protocol by adapting it to an alternative cell-based modeling framework, VirtualLeaf.

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References

  1. Merks RMH, Glazier JA (2005) A cell-centered approach to developmental biology. Phys A 352:113–130

    Article  CAS  Google Scholar 

  2. Anderson ARA, Chaplain MAJ, Rejniak K (2007) Single-cell-based models in biology and medicine. Birkhäuser Verlag, Basel

    Book  Google Scholar 

  3. Hester SD, Belmonte JM, Gens JS et al (2011) A multi-cell, multi-scale model of vertebrate segmentation and somite formation. PLoS Comput Biol 7:e1002155

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  4. Drasdo D, Höhme S (2003) Individual-based approaches to birth and death in avascular tumors. Math Comput Model 37:1163–1175

    Article  Google Scholar 

  5. Alarcón T, Byrne HM, Maini PK (2005) A multiple scale model for tumor growth. Multiscale Model Simul 3:440–475

    Article  Google Scholar 

  6. Kim Y, Stolarska MA, Othmer HG (2007) A hybrid model for tumor spheroid growth in vitro I: theoretical development and early results. Math Models Methods Appl Sci 17:1773–1798

    Article  CAS  Google Scholar 

  7. Macklin P, Edgerton ME, Thompson AM et al (2012) Patient-calibrated agent-based modelling of ductal carcinoma in situ (DCIS): from microscopic measurements to macroscopic predictions of clinical progression. J Theor Biol 301:122–140

    Article  PubMed  PubMed Central  Google Scholar 

  8. Hoehme S, Brulport M, Bauer A et al (2010) Prediction and validation of cell alignment along microvessels as order principle to restore tissue architecture in liver regeneration. Proc Natl Acad Sci U S A 107:10371–10376

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  9. Merks RMH, Guravage M, Inzé D et al (2011) VirtualLeaf: an open-source framework for cell-based modeling of plant tissue growth and development. Plant Physiol 155:656–666

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  10. Hamant O, Heisler MG, Jönsson H et al (2008) Developmental patterning by mechanical signals in Arabidopsis. Science 322:1650–1655

    Article  PubMed  CAS  Google Scholar 

  11. Hirashima T, Iwasa Y, Morishita Y (2009) Dynamic modeling of branching morphogenesis of ureteric bud in early kidney development. J Theor Biol 259:58–66

    Article  PubMed  Google Scholar 

  12. Engelberg JA, Datta A, Mostov KE et al (2011) MDCK cystogenesis driven by cell stabilization within computational analogues. PLoS Comput Biol 7:e1002030

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  13. Merks RMH, Brodsky SV, Goligorksy MS et al (2006) Cell elongation is key to in silico replication of in vitro vasculogenesis and subsequent remodeling. Dev Biol 289:44–54

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  14. Merks RMH, Perryn ED, Shirinifard A et al (2008) Contact-inhibited chemotaxis in de novo and sprouting blood-vessel growth. PLoS Comput Biol 4:e1000163

    Article  PubMed  PubMed Central  Google Scholar 

  15. Bauer AL, Jackson TL, Jiang Y (2007) A cell-based model exhibiting branching and anastomosis during tumor-induced angiogenesis. Biophys J 92:3105–3121

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  16. Bauer AL, Jackson TL, Jiang Y (2009) Topography of extracellular matrix mediates vascular morphogenesis and migration speeds in angiogenesis. PLoS Comput Biol 5:e1000445

    Article  PubMed  PubMed Central  Google Scholar 

  17. Kleinstreuer N, Dix D, Rountree M et al (2013) A computational model predicting disruption of blood vessel development. PLoS Comput Biol 9:e1002996

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  18. Scianna M, Munaron L, Preziosi L (2011) A multiscale hybrid approach for vasculogenesis and related potential blocking therapies. Prog Biophys Mol Biol 106:450–462

    Article  PubMed  CAS  Google Scholar 

  19. Andasari V, Roper RT, Swat MH et al (2012) Integrating intracellular dynamics using CompuCell3D and Bionetsolver: applications to multiscale modelling of cancer cell growth and invasion. PLoS One 7:e33726

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  20. Daub JT, Merks RMH (2013) A cell-based model of extracellular-matrix-guided endothelial cell migration during angiogenesis. Bull Math Biol. doi:10.1007/s11538-013-9826-5

    PubMed Central  Google Scholar 

  21. Palm MM, Merks RMH (2013) Vascular networks due to dynamically arrested crystalline ordering of elongated cells. Phys Rev E 87:012725

    Article  Google Scholar 

  22. Swat MH, Thomas GL, Belmonte JM et al (2012) Multi-scale modeling of tissues using CompuCell3D. In: Asthagiri AR, Arkin AP (eds) Computational methods in cell biology. Academic, Waltham, MA, pp 325–366

    Chapter  Google Scholar 

  23. Glazier JA, Graner F (1993) Simulation of the differential adhesion driven rearrangement of biological cells. Phys Rev E 47:2128–2154

    Article  Google Scholar 

  24. Graner F, Glazier JA (1992) Simulation of biological cell sorting using a two-dimensional extended Potts model. Phys Rev Lett 69:2013–2016

    Article  PubMed  CAS  Google Scholar 

  25. Swat MH, Belmonte J, Heiland RW et al (2012) CompuCell3D Reference Manual Version 3.6.2. http://www.compucell3d.org/BinDoc/cc3d_binaries/Manuals/CompuCell3D_Reference_Manual_v.3.7.2.pdf. Accessed 2 May 2013

  26. Noble WS (2009) A quick guide to organizing computational biology projects. PLoS Comput Biol 5:e1000424

    Article  PubMed  PubMed Central  Google Scholar 

  27. Henderson R (1995) Job scheduling under the portable batch system. In: Feitelson D, Rudolph L (eds) Job scheduling strategies for parallel processing. Springer, Berlin, pp 279–294

    Chapter  Google Scholar 

  28. Merks RMH, Guravage MA (2013) Building simulation models of developing plant organs using VirtualLeaf. In: De Smet I (ed) Plant organogenesis. Springer, New York, pp 333–352

    Chapter  Google Scholar 

  29. Swat MH, Cickovski T, Glazier JA et al (2009) Developers’ documentation for CompuCell3D. http://www.compucell3d.org/BinDoc/cc3d_binaries/Manuals/Developers_Documentation_v3.4.1.pdf Accessed 2 May 2013

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Acknowledgments

We thank Harold Wolff for thoroughly testing the materials and methods discussed in this chapter. We thank the Indiana University and the Biocomplexity Institute for providing the CompuCell3D modeling environment and SARA for providing access to the National Compute Cluster LISA. This work was financed by the Netherlands Consortium for Systems Biology (NCSB), which is part of the Netherlands Genomics Initiative/Netherlands Organisation for Scientific Research. The investigations were in part supported by the Division for Earth and Life Sciences (ALW) with financial aid from the Netherlands Organization for Scientific Research (NWO).

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Correspondence to Roeland M. H. Merks Ph.D. .

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Palm, M.M., Merks, R.M.H. (2015). Large-Scale Parameter Studies of Cell-Based Models of Tissue Morphogenesis Using CompuCell3D or VirtualLeaf . In: Nelson, C. (eds) Tissue Morphogenesis. Methods in Molecular Biology, vol 1189. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-1164-6_20

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  • DOI: https://doi.org/10.1007/978-1-4939-1164-6_20

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-1163-9

  • Online ISBN: 978-1-4939-1164-6

  • eBook Packages: Springer Protocols

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