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
  • Editors' Suggestion
  • Open Access

Feedback between microscopic activity and macroscopic dynamics drives excitability and oscillations in mechanochemical matter

Tim Dullweber1,2, Roman Belousov1, and Anna Erzberger1,2,*

  • *Contact author: anna.erzberger@embl.de

Phys. Rev. E 112, 034411 – Published 19 September, 2025

DOI: https://doi.org/10.1103/mmz3-kbrv

Abstract

The macroscopic behavior of active matter arises from nonequilibrium microscopic processes. In soft materials, active stresses typically drive macroscopic shape changes, which in turn alter the geometry constraining the microscopic dynamics, leading to complex feedback effects. Although such mechanochemical coupling is common in living matter and associated with biological functions such as cell migration, division, and differentiation, the underlying principles are not well understood due to a lack of minimal models that bridge the scales from the microscopic biochemical processes to the macroscopic shape dynamics. To address this gap, we derive tractable coarse-grained equations from microscopic dynamics for a class of mechanochemical systems, in which biochemical signal processing is coupled to shape dynamics. Specifically, we consider molecular interactions at the surface of biological cells that commonly drive cell-cell signaling and adhesion, and obtain a macroscopic description of cells as signal-processing droplets that adaptively change their interfacial tensions. We find a rich phenomenology, including multistability, symmetry-breaking, excitability, and self-sustained shape oscillations, with the underlying critical points revealing universal characteristics of such systems. Our tractable framework provides a paradigm for how soft active materials respond to shape-dependent signals, and suggests novel modes of self-organisation at the collective scale. These are explored further in our companion manuscript [T. Dullweber et al., Phys. Rev. Lett. 135, 128404 (2025)].

View figure in article

Physics Subject Headings (PhySH)

See Also

Shape Switching and Tunable Oscillations of Adaptive Droplets

Tim Dullweber, Roman Belousov, Camilla Autorino, Nicoletta I. Petridou, and Anna Erzberger
Phys. Rev. Lett. 135, 128404 (2025)

Article Text

Supplemental Material

References (111)

  1. É. Fodor and M. C. Marchetti, Physica A 504, 106 (2018).
  2. D. Needleman and Z. Dogic, Nat. Rev. Mater. 2, 17048 (2017).
  3. S. Ramaswamy, J. Stat. Mech. (2017) 054002.
  4. M. C. Marchetti, J.-F. Joanny, S. Ramaswamy, T. B. Liverpool, J. Prost, M. Rao, and R. A. Simha, Rev. Mod. Phys. 85, 1143 (2013).
  5. S. Ray, J. Zhang, and Z. Dogic, Phys. Rev. Lett. 130, 238301 (2023).
  6. A. Goldbeter, Philos. Trans. R. Soc. A 376, 20170376 (2018).
  7. A. Singh, P. Parvin, B. Saha, and D. Das, Nat. Rev. Chem. 8, 723 (2024).
  8. J.-L. Maître and C.-P. Heisenberg, Curr. Biol. 23, R626 (2013).
  9. E. Papusheva and C.-P. Heisenberg, EMBO J. 29, 2753 (2010).
  10. K. E. Kasza, A. C. Rowat, J. Liu, T. E. Angelini, C. P. Brangwynne, G. H. Koenderink, and D. A. Weitz, Curr. Opin. Cell Biol. 19, 101 (2007).
  11. J. Rombouts, J. Elliott, and A. Erzberger, EMBO Rep. 24, e57739 (2023).
  12. C. J. Chan, C.-P. Heisenberg, and T. Hiiragi, Curr. Biol. 27, R1024 (2017).
  13. P. Gross, K. V. Kumar, and S. W. Grill, Annu. Rev. Biophys. 46, 337 (2017).
  14. S. Dupont and S. A. Wickström, Nat. Rev. Genet. 23, 624 (2022).
  15. S. Shamipour, S. Caballero-Mancebo, and C.-P. Heisenberg, Dev. Cell 56, 213 (2021).
  16. M. Nishikawa, S. R. Naganathan, F. Jülicher, and S. W. Grill, Elife 6, e19595 (2017).
  17. M. Mayer, M. Depken, J. S. Bois, F. Jülicher, and S. W. Grill, Nature (London) 467, 617 (2010).
  18. S. K. Vogel, Z. Petrasek, F. Heinemann, and P. Schwille, Elife 2, e00116 (2013).
  19. L. Würthner, A. Goychuk, and E. Frey, Phys. Rev. E 108, 014404 (2023).
  20. T. Burkart, M. C. Wigbers, L. Würthner, and E. Frey, Nat. Rev. Phys. 4, 511 (2022).
  21. A. Datta, S. Ghosh, and J. Kondev, Elife 11, e71365 (2022).
  22. N. Tamemoto and H. Noguchi, Sci. Rep. 10, 19582 (2020).
  23. A. Mietke, F. Jülicher, and I. F. Sbalzarini, Proc. Natl. Acad. Sci. USA 116, 29 (2019).
  24. A. Mietke, V. Jemseena, K. V. Kumar, I. F. Sbalzarini, and F. Jülicher, Phys. Rev. Lett. 123, 188101 (2019).
  25. B. Alberts, R. Heald, A. Johnson, D. Morgan, M. Raff, K. Roberts, and P. Walter, Molecular Biology of the Cell (WW Norton & Company, New York, NY, 2022).
  26. T. Dullweber and A. Erzberger, Curr. Opin. Syst. Biol. 32-33, 100445 (2023).
  27. V. Barone, M. Lang, S. G. Krens, S. J. Pradhan, S. Shamipour, K. Sako, M. Sikora, C. C. Guet, and C.-P. Heisenberg, Dev. Cell 43, 198 (2017).
  28. O. Shaya, U. Binshtok, M. Hersch, D. Rivkin, S. Weinreb, L. Amir-Zilberstein, B. Khamaisi, O. Oppenheim, R. A. Desai, R. J. Goodyear et al., Dev. Cell 40, 505 (2017).
  29. I. Khait, Y. Orsher, O. Golan, U. Binshtok, N. Gordon-Bar, L. Amir-Zilberstein, and D. Sprinzak, Cell Rep. 14, 225 (2016).
  30. D. Sprinzak and S. C. Blacklow, Annu. Rev. Biophys. 50, 157 (2021).
  31. N. Guisoni, R. Martinez-Corral, J. Garcia-Ojalvo, and J. de Navascués, Development 144, 1177 (2017).
  32. R. Cohen, S. Taiber, O. Loza, S. Kasirer, S. Woland, and D. Sprinzak, Sci. Adv. 9, eadd2157 (2023).
  33. N. Dray, L. Mancini, U. Binshtok, F. Cheysson, W. Supatto, P. Mahou, S. Bedu, S. Ortica, E. Than-Trong, M. Krecsmarik et al., Cell Stem Cell 28, 1457 (2021).
  34. A. Erzberger, A. Jacobo, A. Dasgupta, and A. Hudspeth, Nat. Phys. 16, 949 (2020).
  35. R. Priya, S. Allanki, A. Gentile, S. Mansingh, V. Uribe, H.-M. Maischein, and D. Y. Stainier, Nature (London) 588, 130 (2020).
  36. S. Toda, L. R. Blauch, S. K. Tang, L. Morsut, and W. A. Lim, Science 361, 156 (2018).
  37. M. Shamir, Y. Bar-On, R. Phillips, and R. Milo, Cell 164, 1302 (2016).
  38. R. Milo and R. Phillips, Cell Biology by the Numbers (Garland Science, New York, NY, 2015).
  39. T. Wyatt, B. Baum, and G. Charras, Curr. Opin. Cell Biol. 38, 68 (2016).
  40. R. Tran-Son-Tay, D. Needham, A. Yeung, and R. Hochmuth, Biophys. J. 60, 856 (1991).
  41. S. J. Bray, Nat. Rev. Mol. Cell Biol. 17, 722 (2016).
  42. T. Dullweber, R. Belousov, C. Autorino, N. I. Petridou, and A. Erzberger, companion paper, Phys. Rev. Lett. 135, 128404 (2025).
  43. S. Hausberg and M. Röger, Nonlinear Differ. Equations Appl. 25, 17 (2018).
  44. F. Brauns, J. Halatek, and E. Frey, Phys. Rev. X 10, 041036 (2020).
  45. A. B. Ross, J. D. Langer, and M. Jovanovic, Mol. Cell. Proteomics 20, 100016 (2021).
  46. C. Buccitelli and M. Selbach, Nat. Rev. Genet. 21, 630 (2020).
  47. K. Jacobson, P. Liu, and B. C. Lagerholm, Cell 177, 806 (2019).
  48. W. S. Trimble and S. Grinstein, J. Cell Biol. 208, 259 (2015).
  49. S. Ramadurai, A. Holt, V. Krasnikov, G. Van Den Bogaart, J. A. Killian, and B. Poolman, J. Am. Chem. Soc. 131, 12650 (2009).
  50. J. Sankaran, M. Manna, L. Guo, R. Kraut, and T. Wohland, Biophys. J. 97, 2630 (2009).
  51. L. Tveriakhina, G. Scanavachi, E. D. Egan, R. B. D. C. Correia, A. P. Martin, J. M. Rogers, J. S. Yodh, J. C. Aster, T. Kirchhausen, and S. C. Blacklow, Dev. Cell 59, 1425 (2024).
  52. D. T. Gonzales, S. Suraritdechachai, C. Zechner, and T.-Y. D. Tang, ChemSystemsChem 5, e202300029 (2023).
  53. E. Sackmann and A.-S. Smith, Soft Matter 10, 1644 (2014).
  54. U. S. Schwarz and S. A. Safran, Rev. Mod. Phys. 85, 1327 (2013).
  55. A.-S. Smith and U. Seifert, Soft Matter 3, 275 (2007).
  56. A.-S. Smith and U. Seifert, Phys. Rev. E: Stat., Nonlinear, Soft Matter Phys. 71, 061902 (2005).
  57. U. Seifert and R. Lipowsky, Phys. Rev. A 42, 4768 (1990).
  58. J.-L. Maître and C.-P. Heisenberg, Curr. Opin. Cell Biol. 23, 508 (2011).
  59. J.-L. Maître, H. Berthoumieux, S. F. G. Krens, G. Salbreux, F. Jülicher, E. Paluch, and C.-P. Heisenberg, Science 338, 253 (2012).
  60. Y.-S. Chu, W. A. Thomas, O. Eder, F. Pincet, E. Perez, J. P. Thiery, and S. Dufour, J. Cell Biol. 167, 1183 (2004).
  61. B. L. Beckstead, J. C. Tung, K. J. Liang, Z. Tavakkol, M. L. Usui, J. E. Olerud, and C. M. Giachelli, J. Biomed. Mater. Res. Part A 91A, 436 (2009).
  62. E. Seib and T. Klein, Biol. Cell 113, 401 (2021).
  63. E. Vázquez-Ulloa, K.-L. Lin, M. Lizano, and C. Sahlgren, Crit. Rev. Biochem. Mol. Biol. 57, 377 (2022).
  64. V. Kandachar and F. Roegiers, Curr. Opin. Cell Biol. 24, 534 (2012).
  65. M. Santillán, Math. Modell. Nat. Phenom. 3, 85 (2008).
  66. U. Binshtok and D. Sprinzak, Mol. Mech. Notch Signaling 1066, 79 (2018).
  67. F. Corson, L. Couturier, H. Rouault, K. Mazouni, and F. Schweisguth, Science 356, eaai7407 (2017).
  68. J. R. Collier, N. A. Monk, P. K. Maini, and J. H. Lewis, J. Theor. Biol. 183, 429 (1996).
  69. E. V. Rusilowicz-Jones, S. Urbé, and M. J. Clague, Mol. Cell 82, 1414 (2022).
  70. M. X. G. Ilagan, S. Lim, M. Fulbright, D. Piwnica-Worms, and R. Kopan, Sci. Signaling 4, rs7 (2011).
  71. C. J. Fryer, J. B. White, and K. A. Jones, Mol. Cell 16, 509 (2004).
  72. M. Sjöqvist and E. R. Andersson, Dev. Biol. 447, 58 (2019).
  73. R. Olsauskas-Kuprys, A. Zlobin, and C. Osipo, OncoTargets Ther. 6, 943 (2013).
  74. K. Yamamoto, S. Ichbiah, J. Pinto, F. Delbary, N. Goehring, H. Turlier, and G. Charras, bioRxiv (2023).
  75. B. G. Godard, R. Dumollard, E. Munro, J. Chenevert, C. Hebras, A. McDougall, and C.-P. Heisenberg, Dev. Cell 55, 695 (2020).
  76. P. Chugh, A. G. Clark, M. B. Smith, D. A. Cassani, K. Dierkes, A. Ragab, P. P. Roux, G. Charras, G. Salbreux, and E. K. Paluch, Nat. Cell Biol. 19, 689 (2017).
  77. J.-L. Maître, H. Turlier, R. Illukkumbura, B. Eismann, R. Niwayama, F. Nédélec, and T. Hiiragi, Nature (London) 536, 344 (2016).
  78. E. Fischer-Friedrich, A. A. Hyman, F. Jülicher, D. J. Müller, and J. Helenius, Sci. Rep. 4, 6213 (2014).
  79. C. Roffay, C. J. Chan, B. Guirao, T. Hiiragi, and F. Graner, Development 148, dev192773 (2021).
  80. D. Fichtner, B. Lorenz, S. Engin, C. Deichmann, M. Oelkers, A. Janshoff, A. Menke, D. Wedlich, and C. M. Franz, PLoS One 9, e93123 (2014).
  81. E. Sitarska and A. Diz-Muñoz, Curr. Opin. Cell Biol. 66, 11 (2020).
  82. F. N. Arslan, É. Hannezo, J. Merrin, M. Loose, and C.-P. Heisenberg, Curr. Biol. 34, 171 (2024).
  83. D. Fabrèges, B. Corominas-Murtra, P. Moghe, A. Kickuth, T. Ichikawa, C. Iwatani, T. Tsukiyama, N. Daniel, J. Gering, A. Stokkermans et al., Science 386, eadh1145 (2024).
  84. A. N. Pisarchik and A. E. Hramov, Multistability in Physical and Living Systems (Springer, Berlin, 2022), Vol. 2, Chap. 3.
  85. A. Jacobo, A. Dasgupta, A. Erzberger, K. Siletti, and A. Hudspeth, Curr. Biol. 29, 3579 (2019).
  86. N. Blackbeard, S. Osborne, S. O'Brien, and A. Amann, arXiv:1210.4484.
  87. See Supplemental Material at http://link.aps.org/supplemental/10.1103/mmz3-kbrv for a video illustrating the different shape and state dynamics accessible in the phase diagram.
  88. E. Y. Bormashenko, Physics of Wetting: Phenomena and Applications of Fluids on Surfaces (Walter de Gruyter GmbH & Co KG, Berlin, 2017).
  89. J. Binysh, T. R. Wilks, and A. Souslov, Sci. Adv. 8, eabk3079 (2022).
  90. M. Boareto, M. K. Jolly, M. Lu, J. N. Onuchic, C. Clementi, and E. Ben-Jacob, Proc. Natl. Acad. Sci. USA 112, E402 (2015).
  91. X. Shi and J. R. Reimers, Sci. Rep. 8, 2147 (2018).
  92. J. Dubrulle, B. M. Jordan, L. Akhmetova, J. A. Farrell, S.-H. Kim, L. Solnica-Krezel, and A. F. Schier, Elife 4, e05042 (2015).
  93. A. Goldbeter et al., Biochemical Oscillations and Cellular Rhythms (Cambridge University Press, Cambridge, UK, 1997).
  94. J. Lewis, Curr. Biol. 13, 1398 (2003).
  95. J. E. Ferrell, T. Y.-C. Tsai, and Q. Yang, Cell 144, 874 (2011).
  96. N. Nandagopal, L. A. Santat, L. LeBon, D. Sprinzak, M. E. Bronner, and M. B. Elowitz, Cell 172, 869 (2018).
  97. C. S. Simon, S. Rahman, D. Raina, C. Schröter, and A.-K. Hadjantonakis, Dev. Cell 55, 341 (2020).
  98. D. Raina, F. Fabris, L. G. Morelli, and C. Schröter, Development 149, dev199710 (2022).
  99. P. Casani-Galdon and J. Garcia-Ojalvo, Curr. Opin. Cell Biol. 78, 102130 (2022).
  100. I. Schreiber, F. Muzika, and J. Červený, in Proceedings of the 6th International Workshop on Hybrid Systems Biology (HSB'19), Prague, Czech Republic, April 6-7, 2019, Revised Selected Papers 6 (Springer, Berlin, 2019), pp. 30–41.
  101. N. I. Petridou, B. Corominas-Murtra, C.-P. Heisenberg, and E. Hannezo, Cell 184, 1914 (2021).
  102. M. A. McEvoy and N. Correll, Science 347, 1261689 (2015).
  103. D. Luo, A. Maheshwari, A. Danielescu, J. Li, Y. Yang, Y. Tao, L. Sun, D. K. Patel, G. Wang, S. Yang et al., Nature (London) 614, 463 (2023).
  104. D. Shah, B. Yang, S. Kriegman, M. Levin, J. Bongard, and R. Kramer-Bottiglio, Adv. Mater. 33, 2002882 (2021).
  105. G. Sun, R. Zhou, Z. Ma, Y. Li, R. Groß, Z. Chen, and S. Zhao, Nat. Commun. 14, 3476 (2023).
  106. S. Terryn, J. Langenbach, E. Roels, J. Brancart, C. Bakkali-Hassani, Q.-A. Poutrel, A. Georgopoulou, T. G. Thuruthel, A. Safaei, P. Ferrentino et al., Mater. Today 47, 187 (2021).
  107. M. Garrido-Casado, G. Asensio-Juárez, and M. Vicente-Manzanares, Annu. Rev. Cell Dev. Biol. 37, 285 (2021).
  108. A. Dhooge, W. Govaerts, Y. A. Kuznetsov, H. G. E. Meijer, and B. Sautois, Math. Comput. Modell. Dyn. Syst. 14, 147 (2008).
  109. W. R. Inc., Mathematica, Version 13.0 (Champaign, IL, 2021).
  110. S. Lembo, L. Strauss, D. Cheng, J. Vermeil, M. Siggel, M. Toro-Nahuelpan, C. J. Chan, J. Kosinski, M. Piel, O. Du Roure et al., biorxiv (2023).
  111. https://git.embl.de/dullwebe/dullweber2024.

Outline

Information

Sign In to Your Journals Account

Filter

Filter

Article Lookup

Enter a citation