Viscoelastic properties of suspended cells measured with shear flow deformation cytometry

  1. Richard Gerum
  2. Elham Mirzahossein
  3. Mar Eroles
  4. Jennifer Elsterer
  5. Astrid Mainka
  6. Andreas Bauer
  7. Selina Sonntag
  8. Alexander Winterl
  9. Johannes Bartl
  10. Lena Fischer
  11. Shada Abuhattum
  12. Ruchi Goswami
  13. Salvatore Girardo
  14. Jochen Guck
  15. Stefan Schrüfer
  16. Nadine Ströhlein
  17. Mojtaba Nosratlo
  18. Harald Herrmann
  19. Dorothea Schultheis
  20. Felix Rico
  21. Sebastian Johannes Müller
  22. Stephan Gekle
  23. Ben Fabry  Is a corresponding author
  1. York University, Canada
  2. University of Erlangen-Nuremberg, Germany
  3. Aix-Marseille Université, CNRS, U1006 INSERM, France
  4. Max Planck Institute for the Science of Light, Germany
  5. University Hospital Erlangen, Germany
  6. University of Bayreuth, Germany

Abstract

Numerous cell functions are accompanied by phenotypic changes in viscoelastic properties, and measuring them can help elucidate higher-level cellular functions in health and disease. We present a high-throughput, simple and low-cost microfluidic method for quantitatively measuring the elastic (storage) and viscous (loss) modulus of individual cells. Cells are suspended in a high-viscosity fluid and are pumped with high pressure through a 5.8 cm long and 200 μm wide microfluidic channel. The fluid shear stress induces large, near ellipsoidal cell deformations. In addition, the flow profile in the channel causes the cells to rotate in a tank-treading manner. From the cell deformation and tank treading frequency, we extract the frequency-dependent viscoelastic cell properties based on a theoretical framework developed by R. Roscoe that describes the deformation of a viscoelastic sphere in a viscous fluid under steady laminar flow. We confirm the accuracy of the method using atomic force microscopy-calibrated polyacrylamide beads and cells. Our measurements demonstrate that suspended cells exhibit power-law, soft glassy rheological behavior that is cell cycle-dependent and mediated by the physical interplay between the actin filament and intermediate filament networks.

Data availability

The software is available on GitHub, the data are available on Dryad.

The following data sets were generated

Article and author information

Author details

  1. Richard Gerum

    Department of Physics and Astronomy, York University, Toronto, Canada
    Competing interests
    Richard Gerum, is inventor in a patent application on this method (EP22150396.4) alongside SG and BF..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5893-2650
  2. Elham Mirzahossein

    Department of Physics, University of Erlangen-Nuremberg, Erlangen, Germany
    Competing interests
    No competing interests declared.
  3. Mar Eroles

    Turing centre for living systems, Aix-Marseille Université, CNRS, U1006 INSERM, Marseille, France
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3571-0769
  4. Jennifer Elsterer

    Department of Physics, University of Erlangen-Nuremberg, Erlangen, Germany
    Competing interests
    No competing interests declared.
  5. Astrid Mainka

    Department of Physics, University of Erlangen-Nuremberg, Erlangen, Germany
    Competing interests
    No competing interests declared.
  6. Andreas Bauer

    Department of Physics, University of Erlangen-Nuremberg, Erlangen, Germany
    Competing interests
    No competing interests declared.
  7. Selina Sonntag

    Department of Physics, University of Erlangen-Nuremberg, Erlangen, Germany
    Competing interests
    No competing interests declared.
  8. Alexander Winterl

    Department of Physics, University of Erlangen-Nuremberg, Erlangen, Germany
    Competing interests
    No competing interests declared.
  9. Johannes Bartl

    Department of Physics, University of Erlangen-Nuremberg, Erlangen, Germany
    Competing interests
    No competing interests declared.
  10. Lena Fischer

    Department of Physics, University of Erlangen-Nuremberg, Erlangen, Germany
    Competing interests
    No competing interests declared.
  11. Shada Abuhattum

    Biological Optomechanics, Max Planck Institute for the Science of Light, Erlangen, Germany
    Competing interests
    No competing interests declared.
  12. Ruchi Goswami

    Biological Optomechanics, Max Planck Institute for the Science of Light, Erlangen, Germany
    Competing interests
    No competing interests declared.
  13. Salvatore Girardo

    Biological Optomechanics, Max Planck Institute for the Science of Light, Erlangen, Germany
    Competing interests
    No competing interests declared.
  14. Jochen Guck

    Biological Optomechanics, Max Planck Institute for the Science of Light, Erlangen, Germany
    Competing interests
    No competing interests declared.
  15. Stefan Schrüfer

    Institute of Polymer Materials, University of Erlangen-Nuremberg, Erlangen, Germany
    Competing interests
    No competing interests declared.
  16. Nadine Ströhlein

    Department of Physics, University of Erlangen-Nuremberg, Erlangen, Germany
    Competing interests
    No competing interests declared.
  17. Mojtaba Nosratlo

    Department of Physics, University of Erlangen-Nuremberg, Erlangen, Germany
    Competing interests
    No competing interests declared.
  18. Harald Herrmann

    Institute of Neuropathology, University Hospital Erlangen, Erlangen, Germany
    Competing interests
    No competing interests declared.
  19. Dorothea Schultheis

    Institute of Neuropathology, University Hospital Erlangen, Erlangen, Germany
    Competing interests
    No competing interests declared.
  20. Felix Rico

    Turing centre for living systems, Aix-Marseille Université, CNRS, U1006 INSERM, Marseille, France
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7757-8340
  21. Sebastian Johannes Müller

    Department of Physics, University of Bayreuth, Bayreuth, Germany
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6020-4991
  22. Stephan Gekle

    Department of Physics, University of Bayreuth, Bayreuth, Germany
    Competing interests
    Stephan Gekle, is an inventor in a patent application on this method (EP22150396.4)..
  23. Ben Fabry

    Institute of Polymer Materials, University of Erlangen-Nuremberg, Erlangen, Germany
    For correspondence
    ben.fabry@fau.de
    Competing interests
    Ben Fabry, is an inventor in a patent application on this method (EP22150396.4)..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1737-0465

Funding

Deutsche Forschungsgemeinschaft (TRR-SFB 225 subprojects A01,A07 and B07)

  • Elham Mirzahossein

European Union's Horizon 2020 (No 812772)

  • Mar Eroles

European Union's Horizon 2020 (No 953121)

  • Mar Eroles

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2022, Gerum et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Richard Gerum
  2. Elham Mirzahossein
  3. Mar Eroles
  4. Jennifer Elsterer
  5. Astrid Mainka
  6. Andreas Bauer
  7. Selina Sonntag
  8. Alexander Winterl
  9. Johannes Bartl
  10. Lena Fischer
  11. Shada Abuhattum
  12. Ruchi Goswami
  13. Salvatore Girardo
  14. Jochen Guck
  15. Stefan Schrüfer
  16. Nadine Ströhlein
  17. Mojtaba Nosratlo
  18. Harald Herrmann
  19. Dorothea Schultheis
  20. Felix Rico
  21. Sebastian Johannes Müller
  22. Stephan Gekle
  23. Ben Fabry
(2022)
Viscoelastic properties of suspended cells measured with shear flow deformation cytometry
eLife 11:e78823.
https://doi.org/10.7554/eLife.78823

Share this article

https://doi.org/10.7554/eLife.78823

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