, 1:110 | Cite as

Bridging the Scales to Explore Cellular Adaptation and Remodeling

  • Franck J. VernereyEmail author
  • Louis Foucard
  • Mehdi Farsad


This short paper presents a multiscale framework to better understand the mechanisms of biological tissue evolution from molecular to tissue scale. For this, a bottom-up strategy is proposed in which mechano-sensitive molecular processes, the evolution of cell architecture and contraction as well as the interaction between cells and the extra-cellular matrix can be integrated in a single framework. Preliminary studies based on this approach suggest that mechano-sensitive feed-back mechanisms at several length-scales may be a key element to understand tissue adaptivity to tis mechanical environment.


Multiscale modeling Biological tissue Evolution Cells 



FJV gratefully acknowledges the University of Colorado CRCW Seed Grant in support of this research.


  1. 1.
    Baxter, S. C., Morales, M. O., & Goldsmith, E. C. (2008). Adaptive changes in cardiac fibroblast morphology and collagen organization as a result of mechanical environment. Cell Biochemistry and Biophysics, 51(1), 33–44.CrossRefGoogle Scholar
  2. 2.
    Bell, E., Invarsson, B. & Merrill, C. (1979). Production of a tissue-like structure by contraction of collagen lattices by human fibroblasts of different proliferative potential in vitro. Proceedings of the National Academy of Sciences, 76, 1274–1278.CrossRefGoogle Scholar
  3. 3.
    Bischofs, I. B., & Schwarz, U. S. (2003). Cell organization in soft media due to active mechanosensing. Proceedings of the National Academy of Sciences, 100(16), 9274–9279.CrossRefGoogle Scholar
  4. 4.
    Butcher, D. T., Alliston, T., & Weaver, V. M. (2009). A tense situation: Forcing tumour progression. Nature Reviews Cancer, 9, 108–122.CrossRefGoogle Scholar
  5. 5.
    Chrzanowska-Wodnicka, M., & Burridge, K. (1996). Rhostimulated contractility drives the formation of stress fibers and focal adhesions. Journal of Cell Biology, 133(6), 1403–1415.CrossRefGoogle Scholar
  6. 6.
    Costa, K. D., Lee, E. J., & Holmes, J. W. (2003). Creating alignment and anisotropy in engineered heart tissue: Role of boundary conditions in model three-dimensional culture system. Tissue Engineering, 9(4), 567–577.CrossRefGoogle Scholar
  7. 7.
    Dallon, J. C., & Ehrlich, H. P. (2008). A review of fibroblast-populated collagen lattices. Wound Repair and Regeneration, 16, 472–479.CrossRefGoogle Scholar
  8. 8.
    Discher, D. E., Janmey, P., & Wang, Y. (2005). Tissue cells feel and respond to the stiffness of their substrate. Science, 310(5751), 1139–1143.CrossRefGoogle Scholar
  9. 9.
    Dunn, G. A., & Ebendal, T. (1978). Contact guidance on oriented collagen gels. Experimental Cell Research, 111(2), 475–479.Google Scholar
  10. 10.
    Eastwood, M., Mudera, V. C., McGrouther, D. A., & Brown, R. A. (1998). Effect of precise mechanical loading on fibroblast populated collagen lattices: Morphological changes. Cell Motility and the Cytoskeleton, 40(1), 13–21.CrossRefGoogle Scholar
  11. 11.
    Ehrlich, H. P., Gabbiani, G., & Meda, P. (2000). Cell coupling modulates the contraction of fibroblast-populated collagen lattices. Journal of Cellular Physiology, 184(1), 86–92.CrossRefGoogle Scholar
  12. 12.
    Geiger, B., & Bershadsky, A. (2002). Exploring the neighborhood: Adhesion-coupled cell mechanosensors. Cell, 110(2), 139–142.CrossRefGoogle Scholar
  13. 13.
    Harris, A. K., Stopak, D., & Warner, P. (1984). Generation of spatially periodic patterns by a mechanical instability: A mechanical alternative to the turing model. Journal of Embryology and Experimental Morphology, 80, 1–20.Google Scholar
  14. 14.
    Harris, A. K., Stopak, D., & Wild, P. (1980). Fibroblast traction as a mechanism for collagen morphogenesis. Nature, 290, 249–251.CrossRefGoogle Scholar
  15. 15.
    Harris, A. K., Wild, P., & Stopak, D. (1980). Silicone rubber substrata: A new wrinkle in the study of cell locomotion. Science, 208(4440), 177–179.CrossRefGoogle Scholar
  16. 16.
    Haston, W. S., Shields, J. M., & Wilkinson, P. C. (1983). The orientation of fibroblasts and neutrophils on elastic substrata. Experimental Cell Research, 146(1), 117–126.CrossRefGoogle Scholar
  17. 17.
    Hill, A. V. (1938). The heat of shortening and the dynamic constant of muscles. Proceedings of the Royal Society of London, 126(843), 136–195.Google Scholar
  18. 18.
    Huang, S., & Ingber, D. E. (1999). The structural and mechanical complexity of cell-growth control. Nature Cell Biology, 1(5), E131–E138.Google Scholar
  19. 19.
    Lambert, A., Nusgens, B. V., & Lapiere, M. (1998). Mechano-sensing and mechano-reaction of soft connective tissue cells. Advances in Space Research, 21(8/9), 1081–1091.CrossRefGoogle Scholar
  20. 20.
    Makale, M. (2007). Cellular mechanobiology and cancer metastasis. Birth Defects Research (Part C), 81, 329–343.CrossRefGoogle Scholar
  21. 21.
    Martin, P. (1997). Wound healing: Aiming for perfect skin regeneration. Science, 276, 75–81.CrossRefGoogle Scholar
  22. 22.
    Paszek, M., Zahir, N., Johnson, K., Lakins, J., Rozenberg, G., Gefen, A., et al. (2005). Tensional homeostasis and the malignant phenotype. Cancer Cell, 8, 241–254.CrossRefGoogle Scholar
  23. 23.
    Pelham, R. J., & Wang, Y. L. (1997). Cell locomotion and focal adhesions are regulated by substrate flexibility. Proceedings of the National Academy of Sciences of the United States of America, 94, 13661–13665.Google Scholar
  24. 24.
    Rome, L. C., Cook, C., Syme, D. A., Connaughton, M. A., Ashley-Ross, M., Klimov, B., et al. (1999). Trading force for speed: Why superfast crossbridge kinetics leads to superlow forces. Proceedings of the National Academy of Sciences, 96, 5826–5831.CrossRefGoogle Scholar
  25. 25.
    Sawhney, R. K., & Howard, J. (2002). Slow local movements of collagen fibers by fibroblasts drive the rapid global self organization of collagen gels. The Journal of Cell Biology, 157(6), 1083–1091.CrossRefGoogle Scholar
  26. 26.
    Semesh, T., Geiger, B., Bershadsky, A. D., & Kozlov, M. (2005). Focal adhesions as mechanosensors: a physical mechanism. Proceedings of the National Academy of Sciences, 102(35), 12383–12388.CrossRefGoogle Scholar
  27. 27.
    Smith, R. C., Cande, W. Z., Craig, R., Tooth, P. J., Scholey, J. M., & Kendrick-Jones, J. (1983). Regulation of myosin filament assembly by light-chain phosphorylation. Philosophical Transactions of the Royal Society of London, 302(1108),73–82.CrossRefGoogle Scholar
  28. 28.
    Solon, J., Levental, I., Sengupta, K., Georges, P. C., & Janmey, P. A. (2007). Fibroblast adaptation and stiffness matching to soft elastic substrates. Biophysical journal, 93(12), 4453–4461.Google Scholar
  29. 29.
    Sun, D. N., Gu, W. Y., Guo, X. E., Lai, W. M., & Mow, V. C. (2008). A mixed finite element formulation of triphasic mechano-electrochemical theory for charged, hydrated biological soft tissues. International Journal for Numerical Methods in Engineering, 45, 1375–1402.CrossRefGoogle Scholar
  30. 30.
    Tamariz, E., & Grinnell, F. (2002). Modulation of fibroblast morphology and adhesion during collagen matrix remodeling. Molecular Biology of the Cell, 13, 3915–3929.CrossRefGoogle Scholar
  31. 31.
    Vernerey, F. J. (2011). Advances in cell mechanics, on the application of multiphasic theories to the problem of cell-substrate mechanical interactions. New York: Springer.Google Scholar
  32. 32.
    Vernerey, F. J., & Farsad, M. (2011). A constrained mixture approach to mechano-sensing and force generation in contractile cells. Journal of the Mechanical Behavior of Biomedical Materials. doi: 10.1016/j.jmbbm.2011.05.022.
  33. 33.
    Vernerey, F. J., & Farsad, M. (2011). An eulerian/xfem formulation for the large deformation of cortical cell membrane. Computer Methods in Biomechanics and Biomedical Engineering, 14(5), 433–445.CrossRefGoogle Scholar
  34. 34.
    Weiss, P., & Garber, B. (1952). Shape and movement of mesenchyme cells as functions of the physical structure of the medium contributions to a quantitative morphology. Proceedings of the National Academy of Sciences of the United States of America, 38(3), 264–280.Google Scholar
  35. 35.
    Weiss, P., & Garber, B. (1952). Shape and movement of mesenchyme cells as functions of the physical struture of the medium contributions to a quantitative morphology. Proceedings of the National Academy of Sciences, 38, 264–280.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Franck J. Vernerey
    • 1
    Email author
  • Louis Foucard
    • 1
  • Mehdi Farsad
    • 1
  1. 1.Department of Civil, Environmental and Architectural EngineeringUniversity of ColoradoBoulderUSA

Personalised recommendations