Cell-Oriented Modeling of In Vitro Capillary Development

  • Roeland M. H. Merks
  • Stuart A. Newman
  • James A. Glazier
Conference paper
Part of the Lecture Notes in Computer Science book series (LNCS, volume 3305)


We introduce a Cellular Potts model (a cellular-automaton-based Monte-Carlo model) of in vitro capillary development, or angiogenesis. Our model derives from a recent continuum model, which assumes that vascular endothelial cells chemotactically attract each other. Our discrete model is “cell based.” Modeling the cells individually allows us to assign different physicochemical properties to each cell and to study how these properties affect the vascular pattern. Using the model, we assess the roles of intercellular adhesion, cell shape and chemoattractant saturation in in vitro capillary development. We discuss how our computational model can serve as a tool for experimental biologists to “pre-test” hypotheses and to suggest new experiments.


Cell Elongation Dictyostelium Discoideum Monte Carlo Step Local Connectivity Human Umbilical Vascular Endothelial Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Dougherty, E.R., Lotufo, R.A.: Hands-on Morphological Image Processing. Tutorial Texts in Optical Engin., vol. TT59. SPIE Press, Bellingham (2003)Google Scholar
  2. 2.
    Segura, I., Serrano, A., De Buitrago, G.G., Gonzalez, M.A., Abad, J.L., Claveria, C., Gomez, L., Bernad, A., Martinez-A, C., Riese, H.H.: Inhibition of programmed cell death impairs in vitro vascular-like structure formation and reduces in vivo angiogenesis. FASEB J. 16, 833–841 (2002)CrossRefGoogle Scholar
  3. 3.
    Chen, J., Brodsky, S., Li, H., Hampel, D.J., Miyata, T., Weinstein, T., Gafter, U., Norman, J.T., Fine, L.G., Goligorsky, M.S.: Delayed branching of endothelial capillary-like cords in glycated collagen I is mediated by early induction of PAI-1. Am. J. Physiol.-Renal 281, F71–F80 (2001)Google Scholar
  4. 4.
    Namy, P., Ohayon, J., Tracqui, P.: Critical conditions for pattern formation and in vitro tubulogenesis driven by cellular traction fields. J. Theor. Biol. 227, 103–120 (2004)CrossRefMathSciNetGoogle Scholar
  5. 5.
    Gamba, A., Ambrosi, D., Coniglio, A., De Candia, A., Di Talia, S., Giraudo, E., Serini, G., Preziosi, L., Bussolino, F.: Percolation morphogenesis and burgers dynamics in blood vessels formation. Phys. Rev. Lett. 90, 118101 (2003)Google Scholar
  6. 6.
    Serini, G., Ambrosi, D., Giraudo, E., Gamba, A., Preziosi, L., Bussolino, F.: Modeling the early stages of vascular network assembly. EMBO J. 22, 1771–1779 (2003)CrossRefGoogle Scholar
  7. 7.
    Manoussaki, D., Lubkin, S.R., Vernon, R.B., Murray, J.D.: A mechanical model for the formation of vascular networks in vitro. Acta Biotheor. 44, 271–282 (1996)CrossRefGoogle Scholar
  8. 8.
    Manoussaki, D.: A mechanochemical model of angiogenesis and vasculogenesis. ESAIM-Math. Model. Num. 37, 581–599 (2003)zbMATHCrossRefMathSciNetGoogle Scholar
  9. 9.
    Takahashi, K., Ishikawa, N., Sadamoto, Y., Sasamoto, H., Ohta, S., Shiozawa, A., Miyoshi, F., Naito, Y., Nakayama, Y., Tomita, M.: E-cell 2: Multi-platform e-cell simulation system. Bioinformatics 19, 1727–1729 (2003)CrossRefGoogle Scholar
  10. 10.
    Silicon cell project,
  11. 11.
    Savill, N.J., Hogeweg, P.: Modelling morphogenesis: from single cells to crawling slugs. J. Theor. Biol. 184, 229–235 (1997)CrossRefGoogle Scholar
  12. 12.
    Marée, A.F.M., Hogeweg, P.: How amoeboids self-organize into a fruiting body: Multicellular coordination in Dictyostelium discoideum. P. Natl. Acad. Sci. USA 98, 3879–3883 (2001)CrossRefGoogle Scholar
  13. 13.
    Zajac, M., Jones, G.L., Glazier, J.A.: Model of convergent extension in animal morphogenesis. Phys. Rev. Lett. 85, 2022–2025 (2000)CrossRefGoogle Scholar
  14. 14.
    Turner, S., Sherratt, J.A.: Intercellular adhesion and cancer invasion: a discrete simulation using the extended Potts model. J. Theor. Biol. 216, 85–100 (2002)CrossRefMathSciNetGoogle Scholar
  15. 15.
    Kiskowski, M.A., Alber, M.S., Thomas, G.L., Glazier, J.A., Bronstein, N.B., Pu, J., Newman, S.A.: Interplay between activator-inhibitor coupling and cell-matrix adhesion in a cellular automaton model for chondrogenic patterning. Dev. Biol. 271, 372–387 (2004)CrossRefGoogle Scholar
  16. 16.
    Glazier, J.A., Graner, F.: Simulation of the differential adhesion driven rearrangement of biological cells. Phys. Rev. E 47, 2128–2154 (1993)CrossRefGoogle Scholar
  17. 17.
    Izaguirre, J.A., Chaturvedi, R., Huang, C., Cickovski, T., Coffland, J., Thomas, G., Forgacs, G., Alber, M., Hentschel, G., Newman, S.A., Glazier, J.A.: CompuCell, a multi-model framework for simulation of morphogenesis. Bioinformatics 20, 1129–1137 (2004)CrossRefGoogle Scholar
  18. 18.
    Hogeweg, P.: Evolving mechanisms of morphogenesis: on the interplay between differential adhesion and cell differentiation. J. Theor. Biol. 203, 317–333 (2000)CrossRefGoogle Scholar
  19. 19.
    Jiang, Y., Swart, P.J., Saxena, A., Asipauskas, M., Glazier, J.A.: Hysteresis and avalanches in two-dimensional foam rheology simulations. Phys. Rev. E 59, 5819–5832 (1999)CrossRefGoogle Scholar
  20. 20.
    Zajac, M., Jones, G.L., Glazier, J.A.: Simulating convergent extension by way of anisotropic differential adhesion. J. Theor. Biol. 222, 247–259 (2003)CrossRefGoogle Scholar
  21. 21.
    LaRue, A.C., Mironov, V.A., Argraves, W.S., Czirók, A., Fleming, P.A., Drake, C.J.: Patterning of embryonic blood vessels. Dev. Dynam. 228, 21–29 (2003)CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2004

Authors and Affiliations

  • Roeland M. H. Merks
    • 1
    • 2
  • Stuart A. Newman
    • 2
  • James A. Glazier
    • 1
  1. 1.Biocomplexity Institute, Department of PhysicsIndiana UniversityBloomingtonUSA
  2. 2.Cell Biology and AnatomyNew York Medical CollegeValhalla

Personalised recommendations