4.5 Article

Rapid viscoelastic changes are a hallmark of early leukocyte activation

Journal

BIOPHYSICAL JOURNAL
Volume 120, Issue 9, Pages 1692-1704

Publisher

CELL PRESS
DOI: 10.1016/j.bpj.2021.02.042

Keywords

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Categories

Funding

  1. Region Ile de France (DIM Malinf, France)
  2. Labex LaSIPS [ANR-10-LABX-0040-LaSIPS, ANR11-IDEX-0003-02]
  3. CNRS PEPS (France) grant
  4. Ecole Polytechnique (Palaiseau,France)
  5. AXA Research Fund
  6. platform SpICy at Institut de Chimie Physique (France)
  7. Prise de Risques CNRS
  8. ANR JCJC DissecTion
  9. Labex IN-FORM [ANR-11-LABX-0054]
  10. A* MIDEX project - Investissements d'Avenir project - French Government [ANR-11-IDEX-0001-02]
  11. European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant [713750]
  12. Regional Council of Provence-Alpes-Cote d'Azur (France)
  13. A*MIDEX - Investissements d'Avenir project - French Government [ANR-11-IDEX-0001-02]
  14. Inserm (France)
  15. CNRS (France)
  16. Aix-Marseille University (France)
  17. French National Research Agency (France) [ANR-10-IDEX-0001-02 PSL*, ANR11-LABX-0043]
  18. French National Research Agency [ANR-10-INBS-04]
  19. Zeiss France
  20. Spanish Ministry of Economy [BES-2014-068006, BFU2013-48828-P]

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The study found that leukocytes become significantly stiffer and more viscous when stimulated by microbeads mimicking target cells, with these mechanical changes starting within seconds and rapidly evolving over minutes. The elastic and viscous properties of leukocytes evolve in parallel, maintaining a specific ratio that constitutes a mechanical signature unique to each cell type.
To accomplish their critical task of removing infected cells and fighting pathogens, leukocytes activate by forming specialized interfaces with other cells. The physics of this key immunological process are poorly understood, but it is important to understand them because leukocytes have been shown to react to their mechanical environment. Using an innovative micropipette rheometer, we show in three different types of leukocytes that, when stimulated by microbeads mimicking target cells, leukocytes become up to 10 times stiffer and more viscous. These mechanical changes start within seconds after contact and evolve rapidly over minutes. Remarkably, leukocyte elastic and viscous properties evolve in parallel, preserving a well-defined ratio that constitutes a mechanical signature specific to each cell type. Our results indicate that simultaneously tracking both elastic and viscous properties during an active cell process provides a new, to our knowledge, way to investigate cell mechanical processes. Our findings also suggest that dynamic immunomechanical measurements can help discriminate between leukocyte subtypes during activation.

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