Critical conditions for pattern formation and in vitro tubulogenesis driven by cellular traction fields

Patrick Namy, Jacques Ohayon, Philippe Tracqui

Research output: Contribution to journalArticle

80 Scopus citations

Abstract

In vitro angiogenesis assays have shown that tubulogenesis of endothelial cells within biogels, like collagen or fibrin gels, only appears for a critical range of experimental parameter values. These experiments have enabled us to develop and validate a theoretical model in which mechanical interactions of endothelial cells with extracellular matrix influence both active cell migration - haptotaxis - and cellular traction forces. Depending on the number of cells, cell motility and biogel rheological properties, various 2D endothelial patterns can be generated, from non-connected stripe patterns to fully connected networks, which mimic the spatial organization of capillary structures. The model quantitatively and qualitatively reproduces the range of critical values of cell densities and fibrin concentrations for which these cell networks are experimentally observed. We illustrate how cell motility is associated to the self-enhancement of the local traction fields exerted within the biogel in order to produce a pre-patterning of this matrix and subsequent formation of tubular structures, above critical thresholds corresponding to bifurcation points of the mathematical model. The dynamics of this morphogenetic process is discussed in the light of videomicroscopy time lapse sequences of endothelial cells (EAhy926 line) in fibrin gels. Our modeling approach also explains how the progressive appearance and morphology of the cellular networks are modified by gradients of extracellular matrix thickness.

Original languageEnglish (US)
Pages (from-to)103-120
Number of pages18
JournalJournal of Theoretical Biology
Volume227
Issue number1
DOIs
StatePublished - Mar 7 2004

Keywords

  • Angiogenesis modeling
  • Bifurcation
  • Biogel
  • Biomechanical instabilities
  • Cellular traction
  • Endothelial cell network
  • Finite element method

ASJC Scopus subject areas

  • Statistics and Probability
  • Modeling and Simulation
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)
  • Applied Mathematics

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