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Computational Modeling of Angiogenesis: Towards a Multi-Scale Understanding of Cell–Cell and Cell–Matrix Interactions

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Mechanical and Chemical Signaling in Angiogenesis

Part of the book series: Studies in Mechanobiology, Tissue Engineering and Biomaterials ((SMTEB,volume 12))

Abstract

Combined with in vitro and in vivo experiments, mathematical and computational modeling are key to unraveling how mechanical and chemical signaling by endothelial cells coordinates their organization into capillary-like tubes. While in vitro and in vivo experiments can unveil the effects of, for example, environmental changes or gene knockouts, computational models provide a way to formalize and understand the mechanisms underlying these observations. This chapter reviews recent computational approaches to model angiogenesis, and discusses the insights they provide into the mechanisms of angiogenesis. We introduce a new cell-based computational model of an in vitro assay of angiogenic sprouting from endothelial monolayers in fibrin matrices. Endothelial cells are modeled by the Cellular Potts Model, combined with continuum descriptions to model haptotaxis and proteolysis of the extracellular matrix. The computational model demonstrates how a variety of cellular structural properties and behaviors determine the dynamics of tube formation. We aim to extend this model to a multi-scale model in the sense that cells, extracellular matrix and cell-regulation are described at different levels of detail and feedback on each other. Finally we discuss how computational modeling, combined with in vitro and in vivo modeling steers experiments, and how it generates new experimental hypotheses and insights on the mechanics of angiogenesis.

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Acknowledgments

We thank Indiana University and the Biocomplexity Institute for providing the CC3D modeling environment. This work was cofinanced by the Netherlands Consortium for Systems Biology (NCSB) which is part of the Netherlands Genomics Initiative/Netherlands organization for Scientific Research and by the Netherlands Institute of Regenerative Medicine. 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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Authors and Affiliations

  1. Centrum Wiskunde and Informatica, 1098 XG, Amsterdam, The Netherlands

    Sonja E. M. Boas, Margriet M. Palm & Roeland M. H. Merks

  2. Netherlands Consortium for Systems Biology, Netherlands Institute for Systems Biology, 1098 XG, Amsterdam, The Netherlands

    Sonja E. M. Boas, Margriet M. Palm & Roeland M. H. Merks

  3. VU University Medical Center, Van der Boechorststraat 7, Amsterdam, The Netherlands

    Pieter Koolwijk

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  1. Sonja E. M. Boas
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  2. Margriet M. Palm
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  3. Pieter Koolwijk
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  4. Roeland M. H. Merks
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Correspondence to Roeland M. H. Merks .

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Editors and Affiliations

  1. Department of Biomedical Engineering, Cornell Univesity, Ithaca, USA

    Cynthia A. Reinhart-King

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Boas, S.E.M., Palm, M.M., Koolwijk, P., Merks, R.M.H. (2013). Computational Modeling of Angiogenesis: Towards a Multi-Scale Understanding of Cell–Cell and Cell–Matrix Interactions. In: Reinhart-King, C. (eds) Mechanical and Chemical Signaling in Angiogenesis. Studies in Mechanobiology, Tissue Engineering and Biomaterials, vol 12. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-30856-7_8

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  • DOI: https://doi.org/10.1007/978-3-642-30856-7_8

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