Leading edge maintenance in migrating cells is an emergent property of branched actin network growth

  1. Rikki M Garner
  2. Julie A Theriot  Is a corresponding author
  1. Howard Hughes Medical Institute, University of Washington, United States


Animal cell migration is predominantly driven by the coordinated, yet stochastic, polymerization of thousands of nanometer-scale actin filaments across micron-scale cell leading edges. It remains unclear how such inherently noisy processes generate robust cellular behavior. We employed high-speed imaging of migrating neutrophil-like HL-60 cells to explore the fine-scale shape fluctuations that emerge and relax throughout the process of leading edge maintenance. We then developed a minimal stochastic model of the leading edge that reproduces this stable relaxation behavior. Remarkably, we find lamellipodial stability naturally emerges from the interplay between branched actin network growth and leading edge shape - with no additional feedback required - based on a synergy between membrane-proximal branching and lateral spreading of filaments. These results thus demonstrate a novel biological noise-suppression mechanism based entirely on system geometry. Furthermore, our model suggests that the Arp2/3-mediated ~70‑80º branching angle optimally smooths lamellipodial shape, addressing its long-mysterious conservation from protists to mammals.

Data availability

Analysis and modeling code for this paper is available on the Theriot lab Gitlab:<https://gitlab.com/theriot_lab/leading-edge-stability-in-motile-cells-is-an-emergent-property-of-branched-actin-network-growth> under the MIT license. Figure data are available in the Source Data files. The large size of the raw video microscopy data (865 GB of image files in the Open Microscopy Environment OME-TIFF format) and the associated analyzed data (320 GB) prohibits their upload to a public repository. The complete raw and analyzed data files for one example experimental dataset and one example simulated dataset (corresponding to the data shown in Fig. 1a-f and Fig. 2c-j, respectively) are available on Figshare <https://figshare.com/projects/Leading_edge_stability_in_motile_cells_is_an_emergent_property_of_branched_actin_network_growth/132878>. Code to analyze this data are publicly available on Gitlab as noted above. Requests for additional raw or analyzed data should be sent to the corresponding author by email. Data will be made available in the form of a hard drive shipped by mail. There are no restrictions on who may access the data.

Article and author information

Author details

  1. Rikki M Garner

    Department of Biology, Howard Hughes Medical Institute, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9998-4596
  2. Julie A Theriot

    Department of Biology, Howard Hughes Medical Institute, University of Washington, Seattle, United States
    For correspondence
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2334-2535


National Science Foundation

  • Rikki M Garner

Howard Hughes Medical Institute

  • Julie A Theriot

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.


Animal experimentation: Experiments using zebrafish larvae were approved by the University of Washington Institutional Animal Care and Use Committee (protocol 4427-01).

Reviewing Editor

  1. Alphee Michelot, Institut de Biologie du Développement, France

Version history

  1. Preprint posted: August 22, 2020 (view preprint)
  2. Received: October 2, 2021
  3. Accepted: March 9, 2022
  4. Accepted Manuscript published: March 11, 2022 (version 1)
  5. Version of Record published: April 22, 2022 (version 2)
  6. Version of Record updated: May 3, 2022 (version 3)


© 2022, Garner & Theriot

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.


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  1. Rikki M Garner
  2. Julie A Theriot
Leading edge maintenance in migrating cells is an emergent property of branched actin network growth
eLife 11:e74389.

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