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A bottom-up approach to cell mechanics

Nature Physics volume 2, pages 231–238 (2006)Cite this article

Abstract

The mechanical stability and integrity of biological cells is provided by the cytoskeleton, a semidilute meshwork of biopolymers. Recent research has underscored its role as a dynamic, multifunctional muscle, whose passive and active mechanical performance is highly heterogeneous in space and time and intimately linked to many biological functions, such that it may serve as a sensitive indicator for the health or developmental state of the cell. In vitro reconstitution of ‘functional modules’ of the cytoskeleton is now seen as a way of balancing the mutually conflicting demands for simplicity, which is required for systematic and quantitative studies, and for a sufficient degree of complexity that allows a faithful representation of biological functions. This bottom-up strategy, aimed at unravelling biological complexity from its physical basis, builds on the latest advances in technology, experimental design and theoretical modelling, which are reviewed in this progress report.

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Figure 1: Biological Complexity - the structural basis of cell motility
Figure 2: Physical Simplicity - structural phase transitions

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References

  1. Gardel, M. L. et al. Prestressed F-actin networks cross-linked by hinged filamins replicate mechanical prperties of cells. Proc. Natl Acad. Sci. USA 103, 1762–1767 (2006).

    Article  ADS  Google Scholar 

  2. Fabry, B. et al. Scaling the microrheology of living cells. Phys. Rev. Lett. 87, 148102 (2001).

    Article  ADS  Google Scholar 

  3. Fernandez, P., Pullarkat, P. A. & Ott, A. A master relation defines the nonlinear viscoelasticity of single fibroblasts. Biophys. J.doi:10.1529/biophysj.105.072215 (2006).

  4. Guck, J. et al. Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence. Biophys. J. 88, 3689–3698 (2005).

    Article  ADS  Google Scholar 

  5. Svitkina, T. M. et al. Mechanism of filopodia initiation by reorganization of a dendritic network. J. Cell Biol. 160, 409–421 (2003).

    Article  Google Scholar 

  6. Small, J. V., Stradal, T., Vignal, E. & Rottner, K. The lamellipodium: where motilitiy begins. Trends Cell Biol. 12, 112–120 (2002).

    Article  Google Scholar 

  7. Bausch, A. R., Ziemann, F., Boulbitch, A. A., Jacobson, K. & Sackmann, E. Local measurements of viscoelastic parameters of adherent cell surfaces by magnetic bead microrheometry. Biophys. J. 75, 2038–2049 (1998).

    Article  Google Scholar 

  8. Radmacher, M. in Atomic Force Microscopy in Cell Biology (eds Jena, B. P., Horber, J. K. H. & Matsudaira, P. T.) 67–90 (Academic, London, 2002).

    Book  Google Scholar 

  9. Mahaffy, R. E., Shih, C. K., MacKintosh, F. C. & Kas, J. Scanning probe-based frequency-dependent microrheology of polymer gels and biological cells. Phys. Rev. Lett. 85, 880–883 (2000).

    Article  ADS  Google Scholar 

  10. Hartwell, L. H., Hopfield, J. J., Leibler, S. & Murray, A. W. From molecular to modular cell biology. Nature 402, 47–51 (1999).

    Article  Google Scholar 

  11. Mogliner, A. & Rubinstein, B. The physics of vilopodial protrusion. Biophys. J. 89, 782–795 (2005).

    Article  Google Scholar 

  12. Alberts, J. B. & Odell, G. M. In silico reconstitution of listeria propulsion exhibits nano-saltation. PLOS Biol. 2, 2054–2066 (2004).

    Article  Google Scholar 

  13. de Gennes, P. G. Scaling Concepts in Polymer Physics (Cornell Univ. Press, Ithaca and London, 1979).

    Google Scholar 

  14. Morse, D. C. Viscoelasticity of concentrated isotropic solutions of semiflexible polymers. 2. Linear response. Macromolecules 31, 7044–7067 (1998).

    Article  ADS  Google Scholar 

  15. Isambert, H. & Maggs, A. C. Dynamics and rheology of actin solutions. Macromolecules 29, 1036–1040 (1996).

    Article  ADS  Google Scholar 

  16. Hinner, B., Tempel, M., Sackmann, E., Kroy, K. & Frey, E. Entanglement, elasticity, and viscous relaxation of actin solutions. Phys. Rev. Lett. 81, 2614–2617 (1998).

    Article  ADS  Google Scholar 

  17. Gardel, M. L., Valentine, M. T., Crocker, J. C., Bausch, A. R. & Weitz, D. A. Microrheology of entangled F-actin solutions. Phys. Rev. Lett. 91, 158302 (2003).

    Article  ADS  Google Scholar 

  18. Mackintosh, F. C., Kas, J. & Janmey, P. A. Elasticity of semiflexible biopolymer networks. Phys. Rev. Lett. 75, 4425–4428 (1995).

    Article  ADS  Google Scholar 

  19. Shin, J. H., Gardel, M. L., Mahadevan, L., Matsudaira, P. & Weitz, D. A. Relating microstructure to rheology of a bundled and cross-linked F-actin network in vitro. Proc. Natl Acad. Sci. USA 101, 9636–9641 (2004).

    Article  ADS  Google Scholar 

  20. Wilhelm, J. & Frey, E. Elasticity of stiff polymer networks. Phys. Rev. Lett. 91, 108103 (2003).

    Article  ADS  Google Scholar 

  21. Head, D. A., Levine, A. J. & MacKintosh, E. C. Deformation of cross-linked semiflexible polymer networks. Phys. Rev. Lett. 91, 108102 (2003).

    Article  ADS  Google Scholar 

  22. Head, D. A., Levine, A. J. & MacKintosh, F. C. Distinct regimes of elastic response and deformation modes of cross-linked cytoskeletal and semiflexible polymer networks. Phys. Rev. E 68, 061907 (2003).

    Article  ADS  Google Scholar 

  23. Heussinger, C. & Frey, E. Stiff polymers, foams and fiber networks. Phys. Rev. Lett. 96, 017802 (2006).

    Article  ADS  Google Scholar 

  24. Onck, P. R., Koeman, T., van Dillen, T. & van der Giessen, E. The origin of stiffening in cross-linked semiflexible networks. Phys. Rev. Lett. 95, 178102 (2005).

    Article  ADS  Google Scholar 

  25. Gardel, M. L. et al. Elastic behavior of cross-linked and bundled actin networks. Science 304, 1301–1305 (2004).

    Article  ADS  Google Scholar 

  26. Storm, C., Pastore, J. J., MacKintosh, F. C., Lubensky, T. C. & Janmey, P. A. Nonlinear elasticity in biological gels. Nature 435, 191–194 (2005).

    Article  ADS  Google Scholar 

  27. Kruse, K., Joanny, J. F., Jülicher, F., Prost, J. & Sekimoto, K. Generic theory of active polar gels: a paradigm for cytoskeletal dynamics. Eur. Phys. J. E 16, 5–16 (2005).

    Article  Google Scholar 

  28. Ziebert, F. & Zimmermann, W. Nonlinear competition between asters and stripes in filament-motor systems. Eur. Phys. J. E 18, 41–54 (2005).

    Article  Google Scholar 

  29. Liverpool, T. B. & Marchetti, M. C. Bridging the microscopic and the hydrodynamic in active filament solutions. Europhys. Lett. 69, 846–852 (2005).

    Article  ADS  Google Scholar 

  30. Toner, J., Tu, Y. & Ramaswamy, S. Hydrodynamics and phases of flocks. Ann. of Phys. 318, 170–244 (2005).

    Article  ADS  MathSciNet  Google Scholar 

  31. Jingyuan, X. et al. Mechanical properties of actin filament networks depend on preparation, polymerization conditions, and storage of actin monomers. Biophys. J. 74, 2731–2740 (1998).

    Article  Google Scholar 

  32. Le Goff, L., Hallatschek, O., Frey, E. & Amblard, F. Tracer studies on F-actin fluctuations. Phys. Rev. Lett. 89, 258101 (2002).

    Article  ADS  Google Scholar 

  33. Charras, G. T., Yarrow, Y. C., Horton, M. A., Mahadevan, L. & Mitchison, T. J. Non-equilibration of hydrostatic pressure in blebbing cells. Nature 435, 365–369 (2005).

    Article  ADS  Google Scholar 

  34. Gittes, F., Schnurr, B., Olmsted, P. D., MacKintosh, F. C. & Schmidt, C. F. Microscopic viscoelasticity: Shear moduli of soft materials determined from thermal fluctuations. Phys. Rev. Lett. 79, 3286–3289 (1997).

    Article  ADS  Google Scholar 

  35. Gittes, F. & MacKintosh, F. C. Dynamic shear modulus of a semiflexible polymer network. Phys. Rev. E 58, R1241–R1244 (1998).

    Article  ADS  Google Scholar 

  36. Gittes, F., Mickey, B., Nettleton, J. & Howard, J. Flexural rigidity of microtubules and actin filaments measured from thermal fluctuations in shape. J. Cell. Biol. 120, 923–934 (1993).

    Article  Google Scholar 

  37. Morse, D. C. Viscoelasticity of tightly entangled solutions of semiflexible polymers. Phys. Rev. E 58, R1237–R1240 (1998).

    Article  ADS  Google Scholar 

  38. Mohrdieck, C. et al. A theoretical description of elastic pillar substrates in biophysical experiments. ChemPhysChem 6, 1492–1498 (2005).

    Article  Google Scholar 

  39. Liu, J. et al. Microrheology probes length scale dependent rheology. Phys. Rev. Lett. (in the press).

  40. Levine, A. J. & Lubensky, T. C. One- and two-particle microrheology. Phys. Rev. Lett. 85, 1774–1777 (2000).

    Article  ADS  Google Scholar 

  41. Tseng, Y., Schafer, B. W., Almo, S. C. & Wirtz, D. Functional synergy of actin filament cross-linking proteins. J. Biol. Chem. 277, 25609–25616 (2002).

    Article  Google Scholar 

  42. Hosek, M. & Tang, J. X. Polymer-induced bundling of F actin and the depletion force. Phys. Rev. E 69, 051907 (2004).

    Article  ADS  Google Scholar 

  43. Tharmann, R., Claessens, M. M. A. E. & Bausch, A. R. Micro- and macrorheological properties of actin networks effectively crosslinked by depletion forces. Biophys. J. 90, 2622–2627 (2006).

    Article  ADS  Google Scholar 

  44. Borukhov, L., Bruinsma, R. F., Gelbart, W. M. & Liu, A. J. Structural polymorphism of the cytoskeleton: A model of linker-assisted filament aggregation. Proc. Natl Acad. Sci. USA 102, 3673–3678 (2005).

    Article  ADS  Google Scholar 

  45. Tempel, M., Isenberg, G. & Sackmann, E. Temperature-induced sol-gel transition and microgel formation in alpha-actinin cross-linked actin networks: A rheological study. Phys. Rev. E 54, 1802–1810 (1996).

    Article  ADS  Google Scholar 

  46. Tseng, Y., Fedorov, E., McCaffery, J. M., Almo, S. C. & Wirtz, D. Micromechanics and ultrastructure of actin filament networks crosslinked by human fascin: A comparison with alpha-actinin. J. Mol. Biol. 310, 351–366 (2001).

    Article  Google Scholar 

  47. Kierfeld, J., Kuhne, T. & Lipowsky, R. Discontinuous unbinding transitions of filament bundles. Phys. Rev. Lett. 95, 038102 (2005).

    Article  ADS  Google Scholar 

  48. Valentine, M. T. et al. Colloid surface chemistry critically affects multiple particle tracking measurements of biomaterials. Biophys. J. 86, 4004–4014 (2004).

    Article  ADS  Google Scholar 

  49. Shin, J. H., Mahadevan, L., So, P. T. & Matsudaira, P. Bending stiffness of a crystalline actin bundle. J. Mol. Biol. 337, 255–261 (2004).

    Article  Google Scholar 

  50. Howard, J. & Ashmore, J. F. Stiffness of sensory hair bundles in the acculus of the frog. Hear. Res. 23, 93–104 (1986).

    Article  Google Scholar 

  51. Limozin, L. & Sackmann, E. Polymorphism of cross-linked actin networks in giant vesicles. Phys. Rev. Lett. 89, 168103 (2002).

    Article  ADS  Google Scholar 

  52. Claessens, M. M. A. E., Tharmann, R., Kroy, K. & Bausch, A. R. Microstructure and viscoelasticity of confined semiflexible polymer networks. Nature Phys. 2, 186–189 (2006).

    Article  ADS  Google Scholar 

  53. Humphrey, D., Duggan, C., Saha, D., Smith, D. & Kas, J. Active fluidization of polymer networks through molecular motors. Nature 416, 413–416 (2002).

    Article  ADS  Google Scholar 

  54. Le Goff, L., Amblard, F. & Furst, E. M. Motor-driven dynamics in actin-myosin networks. Phys. Rev. Lett. 88, 018101 (2002).

    Article  ADS  Google Scholar 

  55. Nedelec, F. J., Surrey, T., Maggs, A. C. & Leibler, S. Self-organization of microtubules and motors. Nature 389, 305–308 (1997).

    Article  ADS  Google Scholar 

  56. Lau, A. W. C., Hoffman, B. D., Davies, A., Crocker, J. C. & Lubensky, T. C. Microrheology, stress fluctuations, and active behavior of living cells. Phys. Rev. Lett. 91, 198101 (2003).

    Article  ADS  Google Scholar 

  57. Pantaloni, D., Le Clainche, C. & Carlier, M. F. Mechanism of actin-based motility. Science 292, 1502–1506 (2001).

    Article  ADS  Google Scholar 

  58. Marcy, Y., Prost, J., Carlier, M. F. & Sykes, C. Forces generated during actin-based propulsion: A direct measurement by micromanipulation. Proc. Natl Acad. Sci. USA 101, 5992–5997 (2004).

    Article  ADS  Google Scholar 

  59. Vignjevic, D. et al. Mechanism for formation of filopodial-like bundles in vitro. Mol. Biol. Cell 13, 177A–177A (2002).

    Google Scholar 

  60. Amblard, F., Yurke, B., Pargellis, A. & Leibler, S. A magnetic manipulator for studying local rheology and micromechanical properties of biological systems. Rev. Sci. Inst. 67, 818–827 (1996).

    Article  ADS  Google Scholar 

  61. Ziemann, F., Radler, J. & Sackmann, E. Local measurements of viscoelastic moduli of entangled actin networks using an oscillating magnetic bead micro-rheometer. Biophys. J. 66, 2210–2216 (1994).

    Article  ADS  Google Scholar 

  62. Schmidt, F. G., Ziemann, F. & Sackmann, E. Shear field mapping in actin networks by using magnetic tweezers. Eur. Biophys. J. 24, 348–353 (1996).

    Article  Google Scholar 

  63. Crocker, J. C. et al. Two-point microrheology of inhomogeneous soft materials. Phys. Rev. Lett. 85, 888–891 (2000).

    Article  ADS  Google Scholar 

  64. Mason, T. G. & Weitz, D. A. Optical measurements of frequency-dependent linear viscoelastic moduli of complex fluids. Phys. Rev. Lett. 74, 1250–1253 (1995).

    Article  ADS  Google Scholar 

  65. Schmidt, F. G., Hinner, B. & Sackmann, E. Microrheometry underestimates the values of the viscoelastic moduli in measurements on F-actin solutions compared to macrorheometry. Phys. Rev. E 61, 5646–5653 (2000).

    Article  ADS  Google Scholar 

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Acknowledgements

We thank T. M. Svitkina for providing Fig. 1. We also thank Oliver Lieleg and Rainer Tharmann for providing figures and schematics. The work of ARB is supported by SFB413, also the support of the “Fonds der Chemischen Industrie” is gratefully acknowledged.

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Authors and Affiliations

  1. E22-Biophysics, Technische Universität München, James Franck Straße, 85748, Garching, Germany

    A. R. Bausch

  2. Institut für Theoretische Physik, Universität Leipzig, Augustusplatz 10/11, 04109, Leipzig, Germany

    K. Kroy

  3. Hahn-Meitner Institut, Glienicker Straße 100, 14109, Berlin, Germany

    K. Kroy

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Correspondence to A. R. Bausch or K. Kroy.

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Bausch, A., Kroy, K. A bottom-up approach to cell mechanics. Nature Phys 2, 231–238 (2006). https://doi.org/10.1038/nphys260

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