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On atomic force microscopy and the constitutive behavior of living cells

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Abstract

Atomic force microscopy (AFM) is one of many new technologies available to study the mechanical properties and mechanobiological responses of living cells. Despite the widespread usage of this technology, there has been little attempt to develop new theoretical frameworks to interpret the associated data. Rather, most analyses rely on the classical Hertz solution for the indentation of an elastic half-space within the context of linearized elasticity. In contrast, we propose a fully nonlinear, constrained mixture model for adherent cells that allows one to account separately for the contributions of the three primary structural constituents of the cytoskeleton. Moreover, we extend a prior solution for a small indentation superimposed on a finite equibiaxial extension by incorporating in this mixture model for the special case of an initially random distribution of constituents (actin, intermediate filaments, and microtubules). We submit that this theoretical framework will allow an improved interpretation of indentation force–depth data from a sub-class of atomic force microscopy tests and will serve as an important analytical check for future finite element models. The latter will be necessary to exploit further the capabilities of both atomic force microscopy and nonlinear mixture theories for cell behavior.

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Notes

  1. Explicit derivations were carried out for a Mooney–Rivlin material whereby the classical result was confirmed (see Eq. 8 in Humphrey et al. 1991).

References

  • Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P (2002) Molecular biology of the cell. Garland Science, New York

    Google Scholar 

  • Beatty MF, Usmani SA (1975) On the indentation of a highly elastic half-space. Q J Mech Appl Math 28:47–62

    Google Scholar 

  • Briscoe BJ, Sebastian KS, Adams MJ (1994) The effect of indenter geometry on the elastic response to indentation. J Phys D Appl Phys 27:1156–1162

    Google Scholar 

  • Brodland GW, Gordon R (1990) Intermediate filaments may prevent buckling of compressively loaded microtubules. ASME J Biomech Eng 112:319–321

    Google Scholar 

  • Cheng Y, Hartemink CA, Hartwig JH, Dewey CF (2000) Three-dimensional reconstruction of the actin cytoskeleton from stereo images. J Biomech 33:105–113

    Google Scholar 

  • Costa KD, Yin FCP (1999) Analysis of indentation: implications for measuring mechanical properties with atomic force microscopy. ASME J Biomech Eng 121:462–471

    Google Scholar 

  • Fisher NI, Lewis T, Embleton BJJ (1987) Statistical analysis of spherical data. Cambridge University Press, Cambridge

    Google Scholar 

  • Fung YC (2002) Celebrating the inauguration of the journal: biomechanics and modeling in mechanobiology. Biomech Model Mechanobiol 1:3–4

    Google Scholar 

  • Green AE, Rivlin RS, Shield RT (1952) General theory of small elastic deformations superimposed on finite elastic deformations. Proc R Soc Lond 211A:128–154

    Google Scholar 

  • Heidemann SR, Kaech S, Buxbaum RE, Matus A (1999) Direct observations of the mechanical behaviors of cytoskeleton in living fibroblasts. J Cell Biol 145:109–122

    Google Scholar 

  • Herant M, Marganski WA, Dembo M (2003) The mechanics of neutrophils: synthetic modeling of three experiments. Biophys J 84:3389–3413

    Google Scholar 

  • Humphrey JD (2002a) On mechanical modeling of dynamic changes in the structure and properties of adherent cells. Math Mech Sol 7:521–539

    Google Scholar 

  • Humphrey JD (2002b) Cardiovascular solid mechanics: cells, tissues, and organs. Springer, Berlin Heidelberg New York

    Google Scholar 

  • Humphrey JD, Yin FCP (1987) A new constitutive formulation for characterizing the mechanical behavior of soft tissues. Biophys J 52:563–570

    Google Scholar 

  • Humphrey JD, Halperin HR, Yin FCP (1991) Small indentation superimposed on a finite equibiaxial stretch: implications for cardiac mechanics. ASME J Appl Mech 58:1108–1111

    Google Scholar 

  • Janmey PA, Euteneuer U, Traub P, Schliwa M (1991) Viscoelastic properties of vimentin compared with other filamentous biopolymer networks. J Cell Biol 113:155–160

    Google Scholar 

  • Lanir Y (1983) Constitutive equations for fibrous connective tissues. J Biomech 12:423–436

    Google Scholar 

  • Liu X, Pollack GH (2002) Mechanics of F-actin characterized with microfabricated cantilevers. Biophys J 83:2705–2715

    Google Scholar 

  • Mathur AB, Collinsworth AM, Reichert WM, Krauss WE, Truskey GA (2001) Endothelial, cardiac muscle and skeletal muscle exhibit different viscous and elastic properties as determined by atomic force microscopy. J Biomech 34:1545–1553

    Google Scholar 

  • Miyazaki H, Hayashi K (1999) Atomic force microscopic measurement of the mechanical properties of intact endothelial cells in fresh arteries. Med Biol Eng Comput 37:530–536

    Google Scholar 

  • Radmacher M, Tillmann RW, Fritz M, Gaub HE (1992) From molecules to cells: imaging soft samples with the atomic force microscope. Science 257:1900–1904

    Google Scholar 

  • Rajagopal KR, Tao L (1995) Mechanics of mixtures. World Scientific, Singapore

    Google Scholar 

  • Rotsch C, Radmacher M (2000) Drug-induced changes of cytoskeletal structure and mechanics in fibroblasts: an atomic force microscopy study. Biophys J 78:520–535

    Google Scholar 

  • Sato M, Nagayama K, Kataoka N, Sasaki M, Hane K (2000) Local mechanical properties measured by atomic force microscopy for cultured bovine endothelial cells exposed to shear stress. J Biomech 33:127–135

    Google Scholar 

  • Sneddon IN (1965) The relation between load and penetration in the axisymmetric Boussinesq problem for a punch of arbitrary profile. Int J Eng Sci 3:47–57

    Google Scholar 

  • Stamenovic D, Ingber D (2002) Models of cytoskeletal mechanics of adherent cells. Biomech Model Mechanobiol 1:95–108

    Google Scholar 

  • Treloar LRG (1975) The physics of rubber elasticity. Clarendon Press, Oxford

    Google Scholar 

  • Truesdell C, Noll W (1965) The non-linear field theories of mechanics. In: Flugge S (ed) Handbuch der Physik, Vol III/3. Springer, Berlin Heidelberg New York

  • Wakatsuki T, Kolodney MS, Zahalak GI, Elson EL (2000) Cell mechanics studied by a reconstituted model tissue. Biophys J 79:2353–2368

    Google Scholar 

  • Wu HW, Kuhn T, Moy VT (1998) Mechanical properties of L929 cells measured by atomic force microscopy: effects of anticytoskeletal drugs and membrane crosslinking. Scanning 20:389–397

    Google Scholar 

  • Zhu C, Bao G, Wang N (2000) Cell mechanics: mechanical response, cell adhesion, and molecular deformation. Annu Rev Biomed Eng 2: 189–226

    Google Scholar 

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Acknowledgements

This work was supported, in part, by a Special Opportunity Award from the Whitaker Foundation, a grant from the NIH (R01 HL-64372) through its Bioengineering Research Partnerships Program, and NIH grants R01 HL-58690 and HL-62863.

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Correspondence to J. D. Humphrey.

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Na, S., Sun, Z., Meininger, G.A. et al. On atomic force microscopy and the constitutive behavior of living cells. Biomech Model Mechanobiol 3, 75–84 (2004). https://doi.org/10.1007/s10237-004-0051-x

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