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Peer-reviewedCC BY 4.0Science Advances

Cytoplasmic crowding drives intracellular viscoelastic increase during epithelial maturation

  • Gregory Arkowitz1
  • Olivier Destrian1
  • Anis Aggoun2
  • Marc-Antoine Fardin1
  • Pascal Berto2,3,4
  • Gilles Tessier2
  • René-Marc Mège1
  • Jean-François Berret5
  • Benoit Ladoux1,6,7
7 affiliations
  1. 1Université Paris Cité, CNRS, Institut Jacques Monod, F-75013 Paris, France.
  2. 2Sorbonne Université, CNRS, INSERM, Institut de la Vision, 75012 Paris, France.
  3. 3Aix Marseille Université, CNRS, Centrale Marseille, Institut Fresnel, 13013 Marseille, France.
  4. 4Institut Universitaire de France (IUF), 75005 Paris, France.
  5. 5Université Paris Cité, CNRS, Laboratoire Matière et Systèmes Complexes, F-75013 Paris, France.
  6. 6Department of Physics, Friedrich-Alexander Universität Erlangen-Nürnberg, 91058 Erlangen, Germany.
  7. 7Max-Planck-Zentrum für Physik und Medizin and Max Planck Institute for the Science of Light, 91054 Erlangen, Germany.
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Abstract

The cytoplasm is a crowded, active medium whose mechanical properties underpin essential cellular functions, yet how intracellular rheology adapts during tissue maturation remains unclear. Here, we examine the evolution of cytoplasmic viscoelasticity in Madin-Darby canine kidney epithelial monolayers as cell density increases. Using magnetic rotational spectroscopy, an active microrheology technique, we quantify zero-shear viscosity and elastic modulus throughout monolayer maturation. We uncover a substantial enhancement of intracellular viscoelasticity correlated with increasing cell density and a concomitant rise in cellular dry mass concentration. Hyperosmotic perturbations on subconfluent monolayers reproduce this effect, confirming cytoplasmic crowding as a driver of rheological changes. Notably, intracellular viscoelasticity scales linearly with dry mass concentration, suggesting a direct coupling between internal mechanics and cytoplasmic concentration during epithelial maturation. These findings establish a link between tissue-level organization and intracellular mechanics, highlighting cytoplasmic crowding as a regulator of epithelial homeostasis and providing a framework to connect rheology with tissue behavior.

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Cite

BibTeXRIS
BibTeX
@article{arkowitz2026cytoplasmic,
  title = {{Cytoplasmic crowding drives intracellular viscoelastic increase during epithelial maturation}},
  author = {Gregory Arkowitz and Olivier Destrian and Anis Aggoun and Marc-Antoine Fardin and Pascal Berto and Gilles Tessier and René-Marc Mège and Jean-François Berret and Benoit Ladoux},
  journal = {Science Advances},
  year = {2026},
  month = nov,
  doi = {10.1126/sciadv.aeh7786},
  url = {https://www.science.org/doi/abs/10.1126/sciadv.aeh7786},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Cytoplasmic crowding drives intracellular viscoelastic increase during epithelial maturation
AU  - Gregory Arkowitz
AU  - Olivier Destrian
AU  - Anis Aggoun
AU  - Marc-Antoine Fardin
AU  - Pascal Berto
AU  - Gilles Tessier
AU  - René-Marc Mège
AU  - Jean-François Berret
AU  - Benoit Ladoux
PY  - 2026
DA  - 2026/11/04
JO  - Science Advances
DO  - 10.1126/sciadv.aeh7786
UR  - https://www.science.org/doi/abs/10.1126/sciadv.aeh7786
AB  - The cytoplasm is a crowded, active medium whose mechanical properties underpin essential cellular functions, yet how intracellular rheology adapts during tissue maturation remains unclear. Here, we examine the evolution of cytoplasmic viscoelasticity in Madin-Darby canine kidney epithelial monolayers as cell density increases. Using magnetic rotational spectroscopy, an active microrheology technique, we quantify zero-shear viscosity and elastic modulus throughout monolayer maturation. We uncover a substantial enhancement of intracellular viscoelasticity correlated with increasing cell density and a concomitant rise in cellular dry mass concentration. Hyperosmotic perturbations on subconfluent monolayers reproduce this effect, confirming cytoplasmic crowding as a driver of rheological changes. Notably, intracellular viscoelasticity scales linearly with dry mass concentration, suggesting a direct coupling between internal mechanics and cytoplasmic concentration during epithelial maturation. These findings establish a link between tissue-level organization and intracellular mechanics, highlighting cytoplasmic crowding as a regulator of epithelial homeostasis and providing a framework to connect rheology with tissue behavior.
SN  - 2375-2548
ER  -