- Physical Review Journals
All JournalsPhysics Magazine

PRX Life

Reuse & Permissions

It is not necessary to obtain permission to reuse this article or its components as it is available under the terms of the Creative Commons Attribution 4.0 International license. This license permits unrestricted use, distribution, and reproduction in any medium, provided attribution to the author(s) and the published article's title, journal citation, and DOI are maintained. Please note that some figures may have been included with permission from other third parties. It is your responsibility to obtain the proper permission from the rights holder directly for these figures.

Export citation

Export citation

Choose format for download:

Download Citation
  • Open Access

Cell Divisions Imprint Long Lasting Elastic Strain Fields in Epithelial Tissues

Ali Tahaei1, Romina Piscitello-Gómez2, S. Suganthan1, Greta Cwikla3, Jana F. Fuhrmann2,3, Natalie A. Dye2,3, and Marko Popović1,3,4

PDF

PRX Life 3, 043008 – Published 5 November, 2025

DOI: https://doi.org/10.1103/lh3v-v2c9

Abstract

A hallmark of biological tissues, viewed as complex cellular materials, is the active generation of mechanical stresses by cellular processes, such as cell divisions. Each cellular event generates a force dipole that deforms the surrounding tissue. Therefore, a quantitative description of these force dipoles, and their consequences on tissue mechanics, is one of the central problems in understanding the overall tissue mechanics. In this work, we analyze previously published experimental data on fruit fly Drosophila melanogaster wing epithelia to quantitatively describe the deformation fields induced by a cell-scale force dipole. We find that the measured deformation field can be explained by a simple model of wing epithelium as a linearly elastic sheet. This allows us to infer the magnitude and dynamics of the mechanical forces generated by the cell divisions. In particular, we find that cell divisions exert a transient isotropic force dipole field, corresponding to the temporary localization of the cell nucleus to the tissue surface during the division, and traceless-symmetric force dipole field that remains detectable from the tissue strain field for up to about 3.5 h after the division. This is the timescale on which elastic strains are erased by other mechanical processes and therefore it corresponds to the tissue fluidization timescale. In summary, we have developed a method to infer force dipoles induced by cell divisions, by observing the strain field in the surrounding tissues. Using this method we quantitatively characterize mechanical forces generated during a cell division and their effects on the tissue mechanics.

View figure in article

Physics Subject Headings (PhySH)

Article Text

Supplemental Material

References (52)

  1. C.-P. Heisenberg and Y. Bellaïche, Forces in tissue morphogenesis and patterning, Cell 153, 948 (2013).
  2. A. Brugués, E. Anon, V. Conte, J. H. Veldhuis, M. Gupta, J. Colombelli, J. J. Muñoz, G. W. Brodland, B. Ladoux, and X. Trepat, Forces driving epithelial wound healing, Nat. Phys. 10, 683 (2014).
  3. L. LeGoff and T. Lecuit, Mechanical forces and growth in animal tissues, Cold Spring Harbor Perspect. Biol. 8, a019232 (2016).
  4. F. Jülicher and S. Eaton, Emergence of tissue shape changes from collective cell behaviours, Semin. Cell Dev. Biol. 67, 103 (2017).
  5. R. J. Tetley, M. F. Staddon, D. Heller, A. Hoppe, S. Banerjee, and Y. Mao, Tissue fluidity promotes epithelial wound healing, Nat. Phys. 15, 1195 (2019).
  6. B. Aigouy, R. Farhadifar, D. B. Staple, A. Sagner, J.-C. Röper, F. Jülicher, and S. Eaton, Cell flow reorients the axis of planar polarity in the wing epithelium of Drosophila, Cell 142, 773 (2010).
  7. J. Ranft, M. Basan, J. Elgeti, J.-F. Joanny, J. Prost, and F. Jülicher, Fluidization of tissues by cell division and apoptosis, Proc. Natl. Acad. Sci. USA 107, 20863 (2010).
  8. R. Etournay, M. Popović, M. Merkel, A. Nandi, C. Blasse, B. Aigouy, H. Brandl, G. Myers, G. Salbreux, F. Jülicher et al., Interplay of cell dynamics and epithelial tension during morphogenesis of the Drosophila pupal wing, eLife 4, e07090 (2015).
  9. S. Curran, C. Strandkvist, J. Bathmann, M. de Gennes, A. Kabla, G. Salbreux, and B. Baum, Myosin II controls junction fluctuations to guide epithelial tissue ordering, Dev. Cell 43, 480 (2017).
  10. S. Kim, M. Pochitaloff, G. A. Stooke-Vaughan, and O. Campàs, Embryonic tissues as active foams, Nat. Phys. 17, 859 (2021).
  11. W. T. Gibson, J. H. Veldhuis, B. Rubinstein, H. N. Cartwright, N. Perrimon, G. W. Brodland, R. Nagpal, and M. C. Gibson, Control of the mitotic cleavage plane by local epithelial topology, Cell 144, 427 (2011).
  12. Y. Mao, A. L. Tournier, A. Hoppe, L. Kester, B. J. Thompson, and N. Tapon, Differential proliferation rates generate patterns of mechanical tension that orient tissue growth, EMBO J. 32, 2790 (2013).
  13. D. Roellig, S. Theis, A. Proag, G. Allio, B. Bénazéraf, J. Gros, and M. Suzanne, Force-generating apoptotic cells orchestrate avian neural tube bending, Dev. Cell 57, 707 (2022).
  14. J. Firmino, D. Rocancourt, M. Saadaoui, C. Moreau, and J. Gros, Cell division drives epithelial cell rearrangements during gastrulation in chick, Dev. Cell 36, 249 (2016).
  15. D. A. Matoz-Fernandez, E. Agoritsas, J.-L. Barrat, E. Bertin, and K. Martens, Nonlinear rheology in a model biological tissue, Phys. Rev. Lett. 118, 158105 (2017).
  16. L. Bocanegra-Moreno, A. Singh, E. Hannezo, M. Zagorski, and A. Kicheva, Cell cycle dynamics control fluidity of the developing mouse neuroepithelium, Nat. Phys. 19, 1050 (2023).
  17. T. E. Angelini, E. Hannezo, X. Trepat, M. Marquez, J. J. Fredberg, and D. A. Weitz, Glass-like dynamics of collective cell migration, Proc. Natl. Acad. Sci. USA 108, 4714 (2011).
  18. J.-A. Park, J. H. Kim, D. Bi, J. A. Mitchel, N. T. Qazvini, K. Tantisira, C. Y. Park, M. McGill, S.-H. Kim, B. Gweon et al., Unjamming and cell shape in the asthmatic airway epithelium, Nat. Mater. 14, 1040 (2015).
  19. E.-M. Schotz, M. Lanio, J. A. Talbot, and M. L. Manning, Glassy dynamics in three-dimensional embryonic tissues, J. R. Soc. Interface 10, 20130726 (2013).
  20. R. Farhadifar, J.-C. Röper, B. Aigouy, S. Eaton, and F. Jülicher, The influence of cell mechanics, cell-cell interactions, and proliferation on epithelial packing, Curr. Biol. 17, 2095 (2007).
  21. M. Mayer, M. Depken, J. S. Bois, F. Jülicher, and S. W. Grill, Anisotropies in cortical tension reveal the physical basis of polarizing cortical flows, Nature (London) 467, 617 (2010).
  22. I. Bonnet, P. Marcq, F. Bosveld, L. Fetler, Y. Bellaïche, and F. Graner, Mechanical state, material properties and continuous description of an epithelial tissue, J. R. Soc. Interface 9, 2614 (2012).
  23. K. E. Kasza, D. L. Farrell, and J. A. Zallen, Spatiotemporal control of epithelial remodeling by regulated myosin phosphorylation, Proc. Natl. Acad. Sci. USA 111, 11732 (2014).
  24. R. Piscitello-Gómez, F. S. Gruber, A. Krishna, C. Duclut, C. D. Modes, M. Popović, F. Jülicher, N. A. Dye, and S. Eaton, Core PCP mutations affect short-time mechanical properties but not tissue morphogenesis in the Drosophila pupal wing, eLife 12, e85581 (2023).
  25. N. A. Dye, M. Popović, K Venkatesan Iyer, J. F. Fuhrmann, R. Piscitello-Gómez, S. Eaton, and F. Jülicher, Self-organized patterning of cell morphology via mechanosensitive feedback, eLife 10, e57964 (2021).
  26. A. Moriel, Y. Lubomirsky, E. Lerner, and E. Bouchbinder, Extracting the properties of quasilocalized modes in computer glasses: Long-range continuum fields, contour integrals, and boundary effects, Phys. Rev. E 102, 033008 (2020).
  27. R. N. Chacko, F. P. Landes, G. Biroli, O. Dauchot, A. J. Liu, and D. R. Reichman, Elastoplasticity mediates dynamical heterogeneity below the mode coupling temperature, Phys. Rev. Lett. 127, 048002 (2021).
  28. A. Moriel, D. Richard, E. Lerner, and E. Bouchbinder, Elementary processes in dilatational plasticity of glasses, Phys. Rev. Res. 6, 023167 (2024).
  29. J. F. Fuhrmann, A. Krishna, J. Paijmans, C. Duclut, G. Cwikla, S. Eaton, M. Popović, F. Jülicher, C. D. Modes, and N. A. Dye, Active shape programming drives Drosophila wing disc eversion, Sci. Adv. 10, adp0860 (2024).
  30. See Supplemental Material at http://link.aps.org/supplemental/10.1103/lh3v-v2c9 for additional figures and details of the simulations, which contain Refs.  [20, 24, 36].
  31. M. Merkel, R. Etournay, M. Popović, G. Salbreux, S. Eaton, and F. Jülicher, Triangles bridge the scales: Quantifying cellular contributions to tissue deformation, Phys. Rev. E 95, 032401 (2017).
  32. J. D. Eshelby, The determination of the elastic field of an ellipsoidal inclusion, and related problems, Proc. R. Soc. A 241, 376 (1957).
  33. A. Nicolas, E. E. Ferrero, K. Martens, and J.-L. Barrat, Deformation and flow of amorphous solids: Insights from elastoplastic models, Rev. Mod. Phys. 90, 045006 (2018).
  34. We consider only force dipoles that do not exert a net torque.
  35. M. F. Staddon, A. Hernandez, M. J. Bowick, M. Moshe, and M. C. Marchetti, The role of non-affine deformations in the elastic behavior of the cellular vertex model, Soft Matter 19, 3080 (2023).
  36. R. Etournay, M. Merkel, M. Popović, H. Brandl, N. A. Dye, B. Aigouy, G. Salbreux, S. Eaton, and F. Jülicher, TissueMiner: A multiscale analysis toolkit to quantify how cellular processes create tissue dynamics, eLife 5, e14334 (2016).
  37. P. J. Strzyz, M. Matejcic, and C. Norden, Heterogeneity, cell biology and tissue mechanics of pseudostratified epithelia: Coordination of cell divisions and growth in tightly packed tissues, in International Review of Cell and Molecular Biology, International Review of Cell and Molecular Biology Vol. 325, edited by K. W. Jeon (Academic, New York, 2016), Chap. 3, pp. 89–118.
  38. O. Hertwig, Das problem der befruchtung und der isotropiedes eies: Eine theorie der vererbung, Jenaische Zeitschrift für Naturwissenschaften, Jena: Gustav Fischer. (1884).
  39. M. Théry, A. Jiménez-Dalmaroni, V. Racine, M. Bornens, and F. Jülicher, Experimental and theoretical study of mitotic spindle orientation, Nature (London) 447, 493 (2007).
  40. A. Lisica, J. Fouchard, M. Kelkar, T. P. J. Wyatt, J. Duque, A.-B. Ndiaye, A. Bonfanti, B. Baum, A. J. Kabla, and G. T. Charras, Tension at intercellular junctions is necessary for accurate orientation of cell division in the epithelium plane, Proc. Natl. Acad. Sci. USA 119, e2201600119 (2022).
  41. T. C. Middelkoop, J. Neipel, C. E. Cornell, R. Naumann, L. G. Pimpale, F. Jülicher, and S. W. Grill, A cytokinetic ring-driven cell rotation achieves Hertwig's rule in early development, Proc. Natl. Acad. Sci. USA 121, e2318838121 (2024).
  42. T. Sun, Y. Song, D. Teng, Y. Chen, J. Dai, M. Ma, W. Zhang, and J. C. Pastor-Pareja, Atypical laminin spots and pull-generated microtubule-actin projections mediate Drosophila wing adhesion, Cell Rep. 36, 109667 (2021).
  43. J. C. Dyre, Solid-that-flows picture of glass-forming liquids, J. Phys. Chem. Lett. 15, 1603 (2024).
  44. M. Ozawa and G. Biroli, Elasticity, facilitation, and dynamic heterogeneity in glass-forming liquids, Phys. Rev. Lett. 130, 138201 (2023).
  45. A. Tahaei, G. Biroli, M. Ozawa, M. Popović, and M. Wyart, Scaling description of dynamical heterogeneity and avalanches of relaxation in glass-forming liquids, Phys. Rev. X 13, 031034 (2023).
  46. L. Berthier and J. Kurchan, Non-equilibrium glass transitions in driven and active matter, Nat. Phys. 9, 310 (2013).
  47. D. Bi, X. Yang, M. C. Marchetti, and M. L. Manning, Motility-driven glass and jamming transitions in biological tissues, Phys. Rev. X 6, 021011 (2016).
  48. L. M. C. Janssen, Active glasses, J. Phys.: Condens. Matter 31, 503002 (2019).
  49. F. Brauns, N. H. Claussen, M. F. Lefebvre, E. F. Wieschaus, and B. I. Shraiman, The geometric basis of epithelial convergent extension, eLife 13, RP95521 (2024).
  50. B. Aigouy, D. Umetsu, and S. Eaton, Segmentation and quantitative analysis of epithelial tissues, in Drosophila: Methods and Protocols, edited by C. Dahmann (Springer, New York, 2016), pp. 227–239.
  51. N. A. Dye, M. Popović, S. Spannl, R. Etournay, D. Kainmüller, S. Ghosh, E. W. Myers, F. Jülicher, and S. Eaton, Cell dynamics underlying oriented growth of the Drosophila wing imaginal disc, Development 144, 4406 (2017).
  52. C. Duclut, J. Paijmans, M. M. Inamdar, C. D. Modes, and F. Jülicher, Nonlinear rheology of cellular networks, Cells Dev. 168, 203746 (2021).

Outline

Information

PRX Life 3, 043008– Published 5 November, 2025
  • Received 23 August 2024
  • Accepted 16 September 2025
Crossmark - Check for updates button
Creative Commons Logo

Published by the American Physical Society under the terms of the Creative Commons Attribution 4.0 International license. Further distribution of this work must maintain attribution to the author(s) and the published article's title, journal citation, and DOI.

Published by the American Physical Society

Sign In to Your Journals Account

Filter

Filter

Article Lookup

Enter a citation