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High-frequency microrheology reveals cytoskeleton dynamics in living cells

Nature Physics volume 13, pages 771–775 (2017)Cite this article

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Abstract

Living cells are viscoelastic materials, dominated by an elastic response on timescales longer than a millisecond1. On shorter timescales, the dynamics of individual cytoskeleton filaments are expected to emerge, but active microrheology measurements on cells accessing this regime are scarce2. Here, we develop high-frequency microrheology experiments to probe the viscoelastic response of living cells from 1 Hz to 100 kHz. We report the viscoelasticity of different cell types under cytoskeletal drug treatments. On previously inaccessible short timescales, cells exhibit rich viscoelastic responses that depend on the state of the cytoskeleton. Benign and malignant cancer cells revealed remarkably different scaling laws at high frequencies, providing a unique mechanical fingerprint. Microrheology over a wide dynamic range—up to the frequency characterizing the molecular components—provides a mechanistic understanding of cell mechanics.

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Figure 1: High-frequency microrheology of living fibroblasts.
Figure 2: High-frequency microrheology of fibroblasts with altered actin cytoskeleton.
Figure 3: High-frequency microrheology of benign and malignant cancer cells.

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Acknowledgements

The authors thank A. Sergé, M. Lopez and N. Dusetti for generously providing cell lines and for their technical support, L. Borge from the PCC TPR2-Luminy for technical assistance and F. Eghiaian for helpful discussions. This work was supported by Agence National de la Recherche grants BioHSFS ANR-15-CE11-0007, ANR-11-LABX-0054 (Labex INFORM), ANR-11-IDEX-0001-02 (A ∗ MIDEX) and a European Research Council (ERC) Grant #310080 (MEM-STRUCT-AFM).

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  1. Atsushi Miyagi & Simon Scheuring

    Present address: Present address: Departments of Anesthesiology, Physiology and Biophysics, and Biochemistry, Weill Cornell Medical College, 1300 York Ave, New York, New York 10065, USA (A.M., S.S).,

Authors and Affiliations

  1. U1006 INSERM, Aix-Marseille Université, Parc Scientifique et Technologique de Luminy, 163 avenue de Luminy, 13009 Marseille, France

    Annafrancesca Rigato, Atsushi Miyagi, Simon Scheuring & Felix Rico

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  1. Annafrancesca Rigato
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  2. Atsushi Miyagi
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Contributions

A.R. designed and performed the experiments, analysed the data and wrote the manuscript. F.R. designed the experiments, analysed the data and wrote the manuscript. A.M. modified the high-speed-AFM scanner and helped with calibration and experiments. S.S. contributed to designing the experiments and writing the manuscript.

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Correspondence to Felix Rico.

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The authors declare no competing financial interests.

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Rigato, A., Miyagi, A., Scheuring, S. et al. High-frequency microrheology reveals cytoskeleton dynamics in living cells. Nature Phys 13, 771–775 (2017). https://doi.org/10.1038/nphys4104

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