High-frequency microrheology reveals cytoskeleton dynamics in living cells

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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).

Author information

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.

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) doi:10.1038/nphys4104

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