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

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 im...

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Detalles Bibliográficos
Autores principales: Garner, Rikki M, Theriot, Julie A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9033267/
https://www.ncbi.nlm.nih.gov/pubmed/35275060
http://dx.doi.org/10.7554/eLife.74389
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author Garner, Rikki M
Theriot, Julie A
author_facet Garner, Rikki M
Theriot, Julie A
author_sort Garner, Rikki M
collection PubMed
description 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.
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spelling pubmed-90332672022-04-23 Leading edge maintenance in migrating cells is an emergent property of branched actin network growth Garner, Rikki M Theriot, Julie A eLife Cell Biology 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. eLife Sciences Publications, Ltd 2022-03-11 /pmc/articles/PMC9033267/ /pubmed/35275060 http://dx.doi.org/10.7554/eLife.74389 Text en © 2022, Garner and Theriot https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Garner, Rikki M
Theriot, Julie A
Leading edge maintenance in migrating cells is an emergent property of branched actin network growth
title Leading edge maintenance in migrating cells is an emergent property of branched actin network growth
title_full Leading edge maintenance in migrating cells is an emergent property of branched actin network growth
title_fullStr Leading edge maintenance in migrating cells is an emergent property of branched actin network growth
title_full_unstemmed Leading edge maintenance in migrating cells is an emergent property of branched actin network growth
title_short Leading edge maintenance in migrating cells is an emergent property of branched actin network growth
title_sort leading edge maintenance in migrating cells is an emergent property of branched actin network growth
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9033267/
https://www.ncbi.nlm.nih.gov/pubmed/35275060
http://dx.doi.org/10.7554/eLife.74389
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