Literature DB >> 35275060

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

Rikki M Garner1,2, Julie A Theriot2.   

Abstract

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 ~70-80° branching angle optimally smooths lamellipodial shape, addressing its long-mysterious conservation from protists to mammals.
© 2022, Garner and Theriot.

Entities:  

Keywords:  Arp2/3 complex; actin; cell biology; cell motility; human; lamellipodium; modeling; noise suppression; physics of living systems; zebrafish

Mesh:

Substances:

Year:  2022        PMID: 35275060      PMCID: PMC9033267          DOI: 10.7554/eLife.74389

Source DB:  PubMed          Journal:  Elife        ISSN: 2050-084X            Impact factor:   8.713


  81 in total

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Journal:  Proc Natl Acad Sci U S A       Date:  2016-07-01       Impact factor: 11.205

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Authors:  T M Svitkina; A B Verkhovsky; K M McQuade; G G Borisy
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8.  Neutrophil-like HL-60 cells expressing only GFP-tagged β-actin exhibit nearly normal motility.

Authors:  Rikki M Garner; Gemini Skariah; Amalia Hadjitheodorou; Nathan M Belliveau; Andrew Savinov; Matthew J Footer; Julie A Theriot
Journal:  Cytoskeleton (Hoboken)       Date:  2020-02-28

9.  The structural basis of actin filament branching by the Arp2/3 complex.

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  2 in total

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Review 2.  Biochemical and mechanical regulation of actin dynamics.

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Journal:  Nat Rev Mol Cell Biol       Date:  2022-08-02       Impact factor: 113.915

  2 in total

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