Skip to main content
Log in

Cell adhesion mechanisms and stress relaxation in the mechanics of tumours

  • Original Paper
  • Published:
Biomechanics and Modeling in Mechanobiology Aims and scope Submit manuscript

Abstract

Tumour cells usually live in an environment formed by other host cells, extra-cellular matrix and extra-cellular liquid. Cells duplicate, reorganise and deform while binding each other due to adhesion molecules exerting forces of measurable strength. In this paper, a macroscopic mechanical model of solid tumour is investigated which takes such adhesion mechanisms into account. The extracellular matrix is treated as an elastic compressible material, while, in order to define the relationship between stress and strain for the cellular constituents, the deformation gradient is decomposed in a multiplicative way distinguishing the contribution due to growth, to cell rearrangement and to elastic deformation. On the basis of experimental results at a cellular level, it is proposed that at a macroscopic level there exists a yield condition separating the elastic and dissipative regimes. Previously proposed models are obtained as limit cases, e.g. fluid-like models are obtained in the limit of fast cell reorganisation and negligible yield stress. A numerical test case shows that the model is able to account for several complex interactions: how tumour growth can be influenced by stress, how and where it can generate cell reorganisation to release the stress level, how it can lead to capsule formation and compression of the surrounding tissue.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Ambrosi D, Mollica F (2002) On the mechanics of a growing tumour. Int J Eng Sci 40: 1297–1316

    Article  MathSciNet  Google Scholar 

  • Ambrosi D, Mollica F (2004) The role of stress in the growth of a multicell spheroid. J Math Biol 48: 477–499

    Article  MATH  MathSciNet  Google Scholar 

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

    Article  MATH  MathSciNet  Google Scholar 

  • Araujo RP, McElwain DLS (2004) A linear-elastic model of anisotropic tumour growth. Eur J Appl Math 15: 365–384

    Article  MATH  MathSciNet  Google Scholar 

  • Araujo RP, McElwain DLS (2005a) A mixture theory for the genesis of residual stresses in growing tissues. I. A general formulation. SIAM J Appl Math 65: 1261–1284

    Article  MATH  MathSciNet  Google Scholar 

  • Araujo RP, McElwain DLS (2005b) A mixture theory for the genesis of residual stresses in growing tissues, II: Solutions to the biphasic equations for a multicell spheroid. SIAM J Appl Math 65: 1285–1299

    Article  MathSciNet  Google Scholar 

  • Basov IV, Shelukhin VV (1999) Generalized solutions to the equations of compressible Bingham flows. ZAMM 49: 185–192

    Article  MathSciNet  Google Scholar 

  • Baumgartner W, Hinterdorfer P, Ness W, Raab A, Vestweber D, Schindler H, Drenckhahn D (2000) Cadherin interaction probed by atomic force microscopy. Proc Natl Acad Sci USA 97: 4005–4010

    Article  Google Scholar 

  • Breward CJW, Byrne HM, Lewis CE (2002) The role of cell–cell interactions in a two-phase model for avascular tumour growth. J Math Biol 45: 125–152

    Article  MATH  MathSciNet  Google Scholar 

  • Breward CJW, Byrne HM, Lewis CE (2003) A multiphase model describing vascular tumour growth. Bull Math Biol 65: 609–640

    Article  Google Scholar 

  • Buscall R, Mills PDA, Goodwin JW, Lawson DW (1988) Scaling behaviour of the rheology of aggregate networks formed from colloidal particles. J Chem Soc Faraday Trans 84: 4249–4260

    Article  Google Scholar 

  • Byrne HM, King JR, McElwain DLS, Preziosi L (2003) A two-phase model of solid tumour growth. Appl Math Lett 16: 567–573

    Article  MATH  MathSciNet  Google Scholar 

  • Byrne HM, Preziosi L (2004) Modeling solid tumour growth using the theory of mixtures. Math Med Biol 20: 341–366

    Article  Google Scholar 

  • Canetta E, Duperray A, Leyrat A, Verdier C (2005) Measuring cell viscoelastic properties using a force-spectrometer: Influence of the protein–cytoplasm interactions. Biorheology 42: 298–303

    Google Scholar 

  • Caveda L, Martin-Padura I, Navarro P, Breviario F, Corada M, Gulino D, Lampugnani MG, Dejana E (1996) Inhibition of cultured cell growth by vascular endothelial cadherin (cadherin-5/VE-cadherin). J Clin Invest 98: 886–893

    Article  Google Scholar 

  • Chaplain MAJ, Graziano L, Preziosi L (2006) Mathematical modelling of the loss of tissue compression responsiveness and its role in solid tumour development. Math Med Biol 23: 197–229

    Article  MATH  Google Scholar 

  • Chen CY, Byrne HM, King JR (2001) The influence of growth-induced stress from the surrounding medium on the development of multicell spheroids. J Math Biol 43: 191–220

    Article  MATH  MathSciNet  Google Scholar 

  • Cristini V, Lowengrub J, Nie Q (2003) Nonlinear simulation of tumour growth. J Math Biol 46: 191–224

    Article  MATH  MathSciNet  Google Scholar 

  • Forgacs G, Foty RA, Shafrir Y, Steinberg MS (1998) Viscoelastic properties of living embryonic tissues: a quantitative study. Biophys J 74: 2227–2234

    Article  Google Scholar 

  • Franks SJ, Byrne HM, King JR, Underwood JCE, Lewis CE (2003a) Modelling the early growth of ductal carcinoma in situ of the breast. J Math Biol 47: 424–452

    Article  MATH  MathSciNet  Google Scholar 

  • Franks SJ, Byrne HM, Mudhar HS, Underwood JCE, Lewis CE (2003b) Mathematical modelling of comedo ductal carcinoma in situ of the breast. Math Med Biol 20: 277–308

    Article  MATH  Google Scholar 

  • Franks SJ, King JR (2003) Interactions between a uniformly proliferating tumour and its surrounding: uniform material properties. Math Med Biol 20: 47–89

    Article  MATH  Google Scholar 

  • Frieboes H, Zheng X, Sun C-H, Tromberg B, Gatenby R, Cristini V (2006) An integrated computational/experimental model of tumour invasion. Cancer Res 66: 1597–1604

    Article  Google Scholar 

  • Gibson RF (1994) Principles of Composite Material Mechanics. McGraw-Hill, NY, USA

    Google Scholar 

  • Green AE, Naghdi PM (1969) On basic equations for mixtures. Quart J Mech Appl Math 22: 427–438

    Article  MATH  Google Scholar 

  • Helmlinger G, Netti PA, Lichtenbeld HC, Melder RJ, Jain RK (1997) Solid stress inhibits the growth of multicellular tumour spheroids. Nature Biotechnol 15: 778–783

    Article  Google Scholar 

  • Hohenemser K, Prager W (1932) Über die ansätze der mechanik isotroper kontinua. ZAMM 12: 216–226

    Article  Google Scholar 

  • Holmes NH (1986) Finite deformation of soft tissue: analysis of a mixture model in uni-axial compression. J Biomech Eng 108: 372–381

    Article  Google Scholar 

  • Joseph DD (1990) Fluid dynamics of viscoelastic liquids. Springer, Berlin

    MATH  Google Scholar 

  • Jones AF, Byrne HM, Gibson JS, Dold JW (2000) A mathematical model of the stress induced during solid tumour growth. J Math Biol 40: 473–499

    Article  MATH  MathSciNet  Google Scholar 

  • Levenberg S, Yarden A, Kam Z, Geiger B (1999) p27 is involved in N-cadherin-mediated contact inhibition of cell growth and S-phase entry. Oncogene 18: 869–876

    Article  Google Scholar 

  • Malik WA, Prasad SC, Rajagopal KR, Preziosi L (2008) On the modelling of the viscoelastic response of embryonic tissues. Math Mech Solids 13: 81–91

    Article  MATH  MathSciNet  Google Scholar 

  • Macklin P, Lowengrub J (2007) Nonlinear simulation of the effect of the microenvironment on tumour growth. J Theor Biol 245: 677–704

    Article  MathSciNet  Google Scholar 

  • Malvern LE (1969) Introduction of the Mechanics of a Continuous Medium. Prentice Hall Inc., Englewood Cliffs

    Google Scholar 

  • Netti PA, Jain RK (2003) Interstitial transport in solid tumours. In: Preziosi L (eds) Cancer Modelling and Simulation. CRC Press, Chapman Hall, Boca Raton

    Google Scholar 

  • Panorchan P, Thompson MS, Davis KJ, Tseng Y, Konstantopoulos K, Wirtz D (2006) Single-molecule analysis of cadherin-mediated cell–cell adhesion. J Cell Sci 119: 66–74

    Article  Google Scholar 

  • Paszek MJ, Zahir N, Johnson KR, Lakins JN, Rozenberg GI, Gefen A, Reinhart-King CA, Margulies SS, Dembo M, Boettiger D, Hammer DA, Weaver VM (2005) Tensional homeostasis and the malignant phenotype. Cancer Cell 8: 241–254

    Article  Google Scholar 

  • Preziosi L (1989) On an invariance property of the solution to Stokes’ first problem for viscoelastic fluids. J Non-Newtonian Fluid Mech 33: 225–228

    Article  MATH  Google Scholar 

  • Preziosi L, Joseph DD (1987) Stokes’ first problem for viscoelastic fluids. J Non-Newtonian Fluid Mech 25: 239–259

    Article  MATH  Google Scholar 

  • Preziosi L, Tosin A (2009) Multiphase modeling of tumour growth and extracellular matrix interaction: mathematical tools and applications. J Math Biol.. doi:10.1007/s00285-008-0218-7

    MathSciNet  Google Scholar 

  • Roose T, Netti PA, Munn LL, Boucher Y, Jain RK (2003) Solid stress generated by spheroid growth estimated using a linear poroelasticity model. Microvasc Res 66: 204–212

    Article  Google Scholar 

  • Rodriguez EK, Hoger A, McCulloch A (1994) Stress dependent finite growth in soft elastic tissues. J Biomech 27: 455–467

    Article  Google Scholar 

  • Simon BR (1992) Multiphase poroelastic finite element models for soft tissue structures. Appl Mech Rev 45: 191–218

    Article  Google Scholar 

  • Shelukhin VV (2002) Bingham viscoplastic as a limit of non-Newtonian fluids. J Math Fluid Mech 4: 109–127

    Article  MATH  MathSciNet  Google Scholar 

  • Snabre P, Mills P (1996) Rheology of weakly flocculated suspensions of rigid particles. J Phys III France 6: 1811–1834

    Article  Google Scholar 

  • Sun M, Graham JS, Hegedus B, Marga F, Zhang Y, Forgacs G, Grandbois M (2005) Multiple membrane tethers probed by atomic force microscopy. Biophys J 89: 4320–4329

    Article  Google Scholar 

  • Volokh KY (2006) Stresses in growing soft tissues. Acta Biomater 2: 493–504

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Luigi Preziosi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ambrosi, D., Preziosi, L. Cell adhesion mechanisms and stress relaxation in the mechanics of tumours. Biomech Model Mechanobiol 8, 397–413 (2009). https://doi.org/10.1007/s10237-008-0145-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10237-008-0145-y

Keywords

Navigation