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Cytoskeletal remodelling and slow dynamics in the living cell

Nature Materials volume 4, pages 557–561 (2005)Cite this article

Abstract

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.

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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.

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Acknowledgements

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.

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Author notes

  1. Predrag Bursac and Guillaume Lenormand: These authors contributed equally to this work

Authors and Affiliations

  1. Physiology Program, School of Public Health, Harvard University, Boston, 02115, Massachusetts, USA

    Predrag Bursac, Guillaume Lenormand, Madavi Oliver, James P. Butler & Jeffrey J. Fredberg

  2. University of Erlangen-Nuremberg, Institute of Biomedical Technology, Erlangen, D-91054, Germany

    Ben Fabry

  3. Division of Engineering and Applied Sciences, Harvard University, Cambridge, 02138, Massachusetts, USA

    David A. Weitz

  4. Rowland Institute for Science, Harvard University, Cambridge, 02142, Massachusetts, USA

    Virgile Viasnoff

  5. Department of Geriatric and Respiratory Medicine, Tohoku University School of Medicine, Sendai, 980-8574, Japan

    James P. Butler

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Correspondence to Jeffrey J. Fredberg.

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Bursac, P., Lenormand, G., Fabry, B. et al. Cytoskeletal remodelling and slow dynamics in the living cell. Nature Mater 4, 557–561 (2005). https://doi.org/10.1038/nmat1404

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