Letter | Published:

Cytoskeletal remodelling and slow dynamics in the living cell


The cytoskeleton (CSK) is a crowded network of structural proteins that stabilizes cell shape and drives cell motions. Recent studies on the dynamics of the CSK have established that a wide variety of cell types exhibit rheology in which responses are not tied to any particular relaxation times and are thus scale-free1,2,3,4. Scale-free rheology is often found in a class of materials called soft glasses5, but not all materials expressing scale-free rheology are glassy (see plastics, wood, concrete or some metals for example)6. As such, the extent to which dynamics of the CSK might be regarded as glassy remained an open question. Here we report both forced and spontaneous motions of microbeads tightly bound to the CSK of human muscle cells. Large oscillatory shear fluidized the CSK matrix, which was followed by slow scale-free recovery of rheological properties (aging). Spontaneous bead motions were subdiffusive at short times but superdiffusive at longer times; intermittent motions reflecting nanoscale CSK rearrangements depended on both the approach to kinetic arrest and energy release due to ATP hydrolysis. Aging, intermittency, and approach to kinetic arrest establish a striking analogy between the behaviour of the living CSK and that of inert non-equilibrium systems, including soft glasses, but with important differences that are highly ATP-dependent. These mesoscale dynamics link integrative CSK functions to underlying molecular events, and represent an important intersection of topical issues in condensed matter physics and systems biology.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1

    Alcaraz, J. et al. Microrheology of human lung epithelial cells measured by atomic force microscopy. Biophys. J. 84, 2071–2079 (2003).

  2. 2

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

  3. 3

    Desprat, N., Richert, A., Simeon, J. & Asnacios, A. Creep function of a single living cell. Biophys. J. 88, 2224–2233 (2005).

  4. 4

    Lenormand, G., Millet, E., Fabry, B., Butler, J. & Fredberg, J. Linearity and time-scale invariance of the creep function in living cells. J. R. Soc. Interface 1, 91–97 (2004).

  5. 5

    Sollich, P. Rheological constitutive equation for a model of soft glassy materials. Phys. Rev. E 58, 738–759 (1998).

  6. 6

    Findley, W. N., Lai, J. S. & Onaran, K. Creep and Relaxation of Nonlinear Viscoelastic Materials with an Introduction to Linear Viscoelasticity (Dover Publications, Mineola, New York, 1989).

  7. 7

    Weeks, E. R., Crocker, J. C., Levitt, A. C., Schofield, A. & Weitz, D. A. Three-dimensional direct imaging of structural relaxation near the colloidal glass transition. Science 287, 627–631 (2000).

  8. 8

    Parisi, G. Brownian motion. Nature 433, 221 (2005).

  9. 9

    Struick, L. C. E. Physical Aging in Amorphous Polymers and Other Materials (Elsevier, Houston, Texas, 1978).

  10. 10

    Viasnoff, V. & Lequeux, F. Rejuvenation and overaging in a colloidal glass under shear. Phys. Rev. Lett. 89, 065701 (2002).

  11. 11

    Derec, C., Ducouret, G., Ajdari, A. & Lequeux, F. Aging and nonlinear rheology in suspensions of polyethylene oxide-protected silica particles. Phys. Rev. E 67, 061403 (2003).

  12. 12

    Ramos, L. & Cipelletti, L. Ultraslow dynamics and stress relaxation in the aging of a soft glassy system. Phys. Rev. Lett. 87, 245503 (2001).

  13. 13

    Cloitre, M., Borrega, R. & Leibler, L. Rheological aging and rejuvenation in microgel pastes. Phys. Rev. Lett. 85, 4819–4822 (2000).

  14. 14

    An, S. S. et al. Role of heat shock protein 27 in cytoskeletal remodeling of the airway smooth muscle cell. J. Appl. Physiol. 96, 1701–1713 (2004).

  15. 15

    Kucik, D. F., Elson, E. L. & Sheetz, M. P. Forward transport of glycoproteins on leading lamellopodia in locomoting cells. Nature 340, 315–317 (1989).

  16. 16

    Cipelletti, L. et al. Universal non-diffusive slow dynamics in aging soft matter. Faraday Discuss. 123, 237–251 (2003).

  17. 17

    Bissig, H., Romer, S., Cipelletti, L., Trappea, V. & Schurtenberger, P. Intermittent dynamics and hyper-aging in dense colloidal gels. Phys. Chem. Comm. 6, 21–23 (2003).

  18. 18

    Kob, W., Donati, C., Plimpton, S. J., Poole, P. H. & Glotzer, S. C. Dynamical heterogeneities in a supercooled Lennard-Jones liquid. Phys. Rev. Lett. 79, 2827–2830 (1997).

  19. 19

    Weeks, E. R. & Weitz, D. A. Properties of cage rearrangements observed near the colloidal glass transition. Phys. Rev. Lett. 89, 095704 (2002).

  20. 20

    Evans, R. M. L., Cates, M. E. & Sollich, P. Diffusion and rheology in a model of glassy materials. Eur. Phys. J. 10, 705–718 (1999).

  21. 21

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

  22. 22

    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).

  23. 23

    An, S. S., Laudadio, R. E., Lai, J., Rogers, R. A. & Fredberg, J. J. Stiffness changes in cultured airway smooth muscle cells. Am. J. Physiol. Cell Physiol. 283, C792–C801 (2002).

  24. 24

    Stamenovic, D., Suki, B., Fabry, B., Wang, N. & Fredberg, J. J. Rheology of airway smooth muscle cells is associated with cytoskeletal contractile stress. J. Appl. Physiol. 96, 1600–1605 (2004).

  25. 25

    Kurchan, J. In and out of equilibrium. Nature 433, 222–225 (2005).

  26. 26

    Cugliandolo, L. F., Kurchan, J. & Peliti, L. Energy flow, partial equilibration, and effective temperature in systems with slow dynamics. Phys. Rev. E 55, 3898–3914 (1997).

  27. 27

    Trappe, V., Prasad, V., Cipelletti, L., Segre, P. N. & Weitz, D. A. Jamming phase diagram for attractive particles. Nature 411, 772–775 (2001).

  28. 28

    Liu, A. J. & Nagel, S. R. Jamming is not just cool any more. Nature 396, 21–22 (1998).

  29. 29

    Kitano, H. Systems biology: a brief overview. Science 295, 1662–1664 (2002).

  30. 30

    Csete, M. E. & Doyle, J. C. Reverse engineering of biological complexity. Science 295, 1664–1669 (2002).

  31. 31

    Noble, D. Modeling the heart–from genes to cells to the whole organ. Science 295, 1678–1682 (2002).

  32. 32

    Hu, S. et al. Intracellular stress tomography reveals stress focusing and structural anisotropy in cytoskeleton of living cells. Am. J. Physiol. Cell Physiol. 285, C1082–C1090 (2003).

  33. 33

    Valentine, M. T. et al. Investigating the microenviorement of inhomogeneous soft materials with multiple particle tracking. Phys. Rev. E 64, 061506 (2001).

Download references


These studies were supported by the National Institutes of Health, grants HL33009. HL59682 and HL65960. We thank Reynold Panettieri for providing cells and Srboljub M. Mijailovich, John C. Crocker and Steven S. An for helpful discussions.

Author information

Correspondence to Jeffrey J. Fredberg.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Further reading

Figure 1: Aging and rejuvenation in response to applied shear.
Figure 2: Bead position tracked in the plane.
Figure 3: Statistics of spontaneous bead motions.
Figure 4: Physical forces involved in CSK rearrangements.