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Cell directional and chemotaxis in vascular morphogenesis

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An Erratum to this article was published on 01 January 2005

Abstract

In vertebrates, supply of oxygen and nutrients to tissues is carried out by the blood vascular system through capillary networks. Capillary patterns are closely mimicked by endothelial cells cultured on Matrigel, a preparation of basement membrane proteins. On the Matrigel surface, single randomly dispersed endothelial cells self-organize into vascular networks. The network is characterized by a typical length scale, which is independent of the initial mean density of deposed cells \(\bar n\) over a wide range of values of \(\bar n\). We give here a detailed description of a mathematical model of the process which is able to reproduce several qualitative and quantitative features of in vitro vascularization experiments. Cell matter is basically modelled as an elastic fluid subjected to a specific force field depending on the concentration of a chemoattractant factor. Starting from sparse initial data, mimicking the initial conditions realized in laboratory experiments, numerical solutions reproduce characteristic network structures, similar to observed ones, whose average size is theoretically related to the finite range of chemoattractant diffusion. A possible area of application of the model is the design of properly vascularized artificial tissues.

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References

  • Ambrosi, D. and L. Preziosi (2002). On the closure of mass balance models for tumor growth. Math. Mod. Meth. Appl. Sci. 12, 737–754.

    Article  MATH  MathSciNet  Google Scholar 

  • Burgers, J. (1974). The Non-Linear Diffusion Equation, D. Reidel Publ. Co.

  • Byrne, H. M., J. R. King, D. L. S. McElwain and L. Preziosi (2003). Appl. Math. Lett. 16, 567–573.

    Article  MATH  MathSciNet  Google Scholar 

  • Carmeliet, P. (2000). Mechanisms of angiogenesis and arteriogenesis. Nat. Med. 6, 389–395.

    Article  Google Scholar 

  • Cleaver, O. and P. Krieg (1998). VEGF mediates angioblast migration during development of the dorsal aorta in Xenopus. Development 125, 3905–3914.

    Google Scholar 

  • Di Talia, S., A. Gamba, F. Lamberti and G. Serini. Role of inhibiting factors in mascularization dynamics, in preparation.

  • Folkman, J. and C. Haudenschild (1980). Angiogenesis in vitro. Nature 288, 551–556.

    Article  Google Scholar 

  • Fong, G., L. Zhang, D. Bryce and J. Peng (1999). Increased hemangioblast commitment, not vascular disorganization, is the primary defect in flt-1 knockout mice. Development 126, 3015–3025.

    Google Scholar 

  • Gamba, A., D. Ambrosi, A. Coniglio, A. de Candia, S. Di Talia, E. Giraudo, G. Serini, L. Preziosi and F. Bussolino (2003). Percolation, morphogenesis, and Burgers dynamics in blood vessels formation. Phys. Rev. Lett. 90, 118101.

    Google Scholar 

  • Gazit, Y., D. A. Berk, M. Leunig, L. T. Baxter and R. K. Jain (1995). Scale-invariant behavior and vascular network formation in normal and tumor tissue. Phys. Rev. E 75, 2428–2431.

    Google Scholar 

  • Gengrinovitch, S., B. Berman, G. David, L. Witte, G. Neufeld and D. Ron (1999). Glypican-1 is a VEGF165 binding proteoglycan that acts as an extracellular chaperone for VEGF165. J. Biol. Chem. 274, 10816–10822.

    Google Scholar 

  • Grant, D., K. Tashiro, B. Segui-Real, Y. Yamada, G. Martin and H. Kleinman (1989). Two different laminin domains mediate the differentiation of human endothelial cells into capillary-like structures in vitro. Cell 58, 933–943.

    Article  Google Scholar 

  • Gurbatov, S., A. Malakhov and A. Saichev (1991). Non-Linear Random Waves and Turbulence in Nondispersive Media: Waves, Rays, Particles, Manchester: Manchester United Press.

    Google Scholar 

  • Guyton, A. and J. Hall (2000). Textbook of Medical Physiology, St. Louis: W.B. Saunders.

    Google Scholar 

  • Helmlinger, G., M. Endo, N. Ferrara, L. Hlatky and R. Jain (2000). Formation of endothelial cell networks. Nature 405, 139–141.

    Article  Google Scholar 

  • Hillen, T. and H. Othmer (2000). Chemotaxis equations from the parabolic limit of velocity jump processes. SIAM J. Appl. Math. 61, 751–775.

    Article  MATH  MathSciNet  Google Scholar 

  • Holmes, M. and B. Sleeman (2000). A mathematical model of tumor angiogenesis incorporating cellular traction and viscoelastic effects. J. Theor. Biol. 202, 95–112.

    Article  Google Scholar 

  • Keller, E. F. and L. A. Segel (1970). Initiation of slime mold aggregation viewed as an instability. J. Theor. Biol. 26, 399–415.

    Article  Google Scholar 

  • Kubota, Y., H. Kleinman, G. Martin and T. Lawley (1988). Role of laminin and basement membrane in the morphological differentiation of human endothelial cells into capillary-like structures. J. Cell. Biol. 107, 1589–1598.

    Article  Google Scholar 

  • LeVeque, R. (1990). Numerical Methods for Conservation Laws, Zurich: Birkhauser.

    MATH  Google Scholar 

  • Manoussaki, D., S. R. Lubkin, R. B. Vernon and J. D. Murray (1996). A mechanical model for the formation of vascular networks in vitro. Acta Biotheor. 44, 271–282.

    Article  Google Scholar 

  • Mardia, K. and P. Jupp (1999). Directional Statistics, John Wiley & Sons.

  • Muller, Y., H. Christinger, B. Keyt and A. de Vos (1997). The crystal structure of vascular endothelial growth factor (VEGF) refined to 1.93 Å resolution: multiple copy flexibility and receptor binding. Structure 5, 1325.

    Article  Google Scholar 

  • Murray, J. and G. Oster (1984). Cell traction models for generation of pattern and form in morphogenesis. J. Math. Biol. 19, 265–279.

    MATH  MathSciNet  Google Scholar 

  • Ngwa, G. and P. Maini (1995). Spatio-temporal patterns in a mechanical model for mesenchymal morphogenesis. J. Math. Biol. 33, 489–520.

    Article  MATH  MathSciNet  Google Scholar 

  • Othmer, H. and T. Hillen (2002). Chemotaxis equations from the diffusion limit of transport equations. SIAM J. Appl. Math. 62, 1222–1250.

    Article  MATH  MathSciNet  Google Scholar 

  • Othmer, H. and A. Stevens (1997). Aggregation, blowup and collapse: the ABC’s of generalized taxis. SIAM J. Appl. Math. 57, 1044–1081.

    Article  MATH  MathSciNet  Google Scholar 

  • Pluen, A., P. A. Netti, R. K. Jain and D. A. Berk (1999). Diffusion of macromolecules in agarose gels: comparison of linear and globular configurations. Biophys. J. 77, 542–552.

    Google Scholar 

  • Richardson, T., M. Peters, A. Ennett and D. Mooney (2001). Functional small-diameter neovessels created using endothelial progenitor cells expanded ex vivo. Nat. Biotech. 19, 1029–1034.

    Article  Google Scholar 

  • Ruhrberg, C., H. Gerhardt, M. Golding, R. Watson, S. Ioannidou, H. Fujisawa, C. Betsholtz and D. Shima (2002). Spatially restricted patterning cues provided by heparin-binding VEGF-A control blood vessel branching morphogenesis. Gen. Dev. 16, 2684–2698.

    Article  Google Scholar 

  • Serini, G., D. Ambrosi, E. Giraudo, A. Gamba, L. Preziosi and F. Bussolino (2003). Modeling the early stages of vascular network assembly. EMBO J. 22, 1771–1779.

    Article  Google Scholar 

  • Shandarin, S. and Y. Zeldovich (1989). The large-scale structure of the universe: turbulence, intermittency, structures in a self-gravitating medium. Rev. Mod. Phys. 61, 185–220.

    Article  MathSciNet  Google Scholar 

  • Stauffer, D. and A. Aharony (1994). Introduction to Percolation Theory, London: Taylor & Francis.

    Google Scholar 

  • Vasiev, B. and C. J. Weijer (1999). Modelling chemotactic cell sorting during Dictyostelium discoideum mound formation. Biophys. J. 76, 595–605.

    Article  Google Scholar 

  • Velázquez, J. J. L. (2002). Stability of some mechanisms of chemotactic aggregation. SIAM J. Appl. Math. 5, 1581–1633.

    Article  MATH  Google Scholar 

  • Vergassola, M., B. Dubrulle, U. Frisch and A. Noullez (1994). Burgers’ equation, devil’s staircases and the mass distribution for large-scale structures. Astron. Astrophys. 289, 325–356.

    Google Scholar 

  • Vernon, R., J. Angello, M.-L. Iruela-Arispe, T. Lane and E.-H. Sage (1992). Reorganization of basement membrane matrices by cellular traction promotes the formation of cellular networks in vitro. Lab. Invest. 66, 536–546.

    Google Scholar 

  • Walter, M., W. Cook, S. Ealick, T. Nagabhushan, P. Trotta and C. Bugg (1992). Three-dimensional structure of recombinant human granulocyte-macrophage colony-stimulating factor. J. Mol. Biol. 224, 1075.

    Article  Google Scholar 

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Correspondence to A. Gamba.

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An erratum to this article is available at http://dx.doi.org/10.1016/j.bulm.2005.01.001.

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Ambrosi, D., Gamba, A. & Serini, G. Cell directional and chemotaxis in vascular morphogenesis. Bull. Math. Biol. 66, 1851–1873 (2004). https://doi.org/10.1016/j.bulm.2004.04.004

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  • DOI: https://doi.org/10.1016/j.bulm.2004.04.004

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