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Feedback between F-actin organization and active stress governs criticality and energy localization in the cell cytoskeleton

Nature Physics volume 21, pages 1290–1302 (2025)Cite this article

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Abstract

Self-organized criticality can occur in earthquakes, avalanches and biological processes, and is characterized by intermittent, scale-free energy dissipation. In living cells, the actin cytoskeleton undergoes dynamic structural reorganization, particularly during migration and division, where molecular motors generate mechanical stresses that drive large dissipative events. However, the mechanisms governing these critical transitions remain unclear. Here we show that cytoskeletal criticality emerges from the interplay between F-actin organization and active stress generation. Our study focuses on a minimal actomyosin system in vitro, which is composed of F-actin filaments, myosin II motors and nucleation-promoting factors. By systematically varying the actin connectivity and nematic order, we demonstrate that ordered and sparsely connected networks exhibit exponential stress dissipation, whereas disordered and highly connected networks show heavy-tailed distributions of energy release and the 1/f noise characteristic of self-organized criticality. Increased disorder leads to stress localization, shifting force propagation into stiffer mechanical modes, reminiscent of Anderson localization in condensed-matter systems. Furthermore, we show that network architecture directly regulates the myosin II filament size, establishing a chemical–mechanical feedback loop that modulates criticality. Our findings provide insights into the collective cytoskeletal dynamics, energy localization and cellular self-organization.

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Fig. 1: Actomyosin dynamics exhibit temporal criticality.
Fig. 2: F-actin architecture governs critical behaviour under myosin activity.
Fig. 3: Myosin motion follows a Lévy α distribution independent of the F-actin architecture.
Fig. 4: Criticality is determined by feedback between the F-actin architecture and myosin thick filament size.
Fig. 5: Branched F-actin networks dissipate energy through localized stiff modes.

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Source data are provided with this paper. Raw data supporting the findings of this paper are available from the corresponding author upon reasonable request.

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Codes supporting the findings of this paper are available from the corresponding author upon reasonable request.

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Acknowledgements

We are grateful for insightful discussions with C. O’Hern, M. Shattuck and J. (J.) Treado. We acknowledge the initial contribution related to this project by C. Muresan, A. Pasha Tabatabai and L. Lanier. This work was supported by funding through ARO MURI W911NF-14-1-0403, National Institutes of Health (NIH) R01 1R01GM126256, NIH U54 CA209992 and Human Frontiers Science Program (HFSP) grant no. RGY0073/2018 to M.M. We acknowledge the University of Maryland supercomputing resources (https://hpcc.umd.edu) made available for conducting the computational research reported in this paper.

Author information

Authors and Affiliations

  1. Department of Physics, Yale University, New Haven, CT, USA

    Zachary Gao Sun & Michael Murrell

  2. Systems Biology Institute, Yale University, West Haven, CT, USA

    Zachary Gao Sun & Michael Murrell

  3. Integrated Graduate Program in Physical and Engineering Biology, Yale University, New Haven, CT, USA

    Zachary Gao Sun & Michael Murrell

  4. Institute for Physical Science and Technology, University of Maryland, College Park, MD, USA

    Nathan Zimmerberg & Patrick Kelly

  5. Biophysics Program, University of Maryland, College Park, MD, USA

    Nathan Zimmerberg

  6. Chemical Physics Program, University of Maryland, College Park, MD, USA

    Patrick Kelly

  7. The James Franck Institute, The University of Chicago, Chicago, IL, USA

    Carlos Floyd

  8. Department of Chemistry and Biochemistry, University of Maryland, College Park, MD, USA

    Garegin Papoian

  9. Department of Biomedical Engineering, Yale University, New Haven, CT, USA

    Michael Murrell

Authors
  1. Zachary Gao Sun
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  2. Nathan Zimmerberg
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Contributions

Z.G.S. and M.M. designed and conceived the work and drafted the paper. Z.G.S., M.M., C.F. and N.Z. edited the paper. Z.G.S. performed the experiments. Z.G.S. analysed the experimental data. N.Z. and P.K. performed the simulations. Z.G.S., N.Z. and P.K. analysed the simulation data. M.M. and G.P. supervised the work.

Corresponding author

Correspondence to Michael Murrell.

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Nature Physics thanks Yu Shi and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary information

Supplementary Information

Supplementary Figs. 1–14, description of the simulation model and captions for Supplementary Videos.

Reporting Summary

Supplementary Video 1

0.74-nM Arp2/3-nucleated F-actin deformed by MTFs.

Supplementary Video 2

0.74-nM Arp2/3-nucleated F-actin deformed by MTF composite.

Supplementary Video 3

MEDYAN simulation of Rarp = 0.002 F-actin deformed by MTFs.

Supplementary Video 4

MEDYAN simulation of Rarp = 0.02 F-actin deformed by MTFs.

Supplementary Video 5

MEDYAN simulation of Rarp = 0.004 F-actin filament large bending by MTFs.

Supplementary Video 6

MEDYAN simulation of Rarp = 0.02 F-actin filament large bending by MTFs.

Supplementary Video 7

MEDYAN simulation of Rarp = 0.02 F-actin filament large displacements and energy release over time.

Source data

Source Data Figs. 1–5

Source data for Figs. 1–5.

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Sun, Z.G., Zimmerberg, N., Kelly, P. et al. Feedback between F-actin organization and active stress governs criticality and energy localization in the cell cytoskeleton. Nat. Phys. 21, 1290–1302 (2025). https://doi.org/10.1038/s41567-025-02919-4

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