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An energy-based mathematical model of actin-driven protrusions in eukaryotic chemotaxis

Abstract:
In eukaryotic cell chemotaxis, cells extend and retract transient actin-driven protrusions at their membrane that facilitate both the detection of external chemical gradients and directional movement via the formation of focal adhesions with the extracellular matrix. Although extensive experimental work has detailed how cellular protrusions and morphology vary under different environmental conditions, the mechanistic principles linking protrusive activity to these factors remain poorly understood. Here, we model the extension of actin-based protrusions in chemotaxis as an optimisation problem, wherein cells balance the detection of chemical gradients with the energetic cost of protrusion formation. Our model, built on the assumption of energy minimisation, provides a framework that successfully reproduces experimentally observed patterns of protrusive activity across a range of biological systems and environmental conditions, suggesting that energetic efficiency may underpin the morphology and chemotactic behaviour of motile eukaryotic cells. Additionally, we leverage the model to generate novel predictions regarding cellular responses to other, experimentally untested environmental perturbations, providing testable hypotheses for future experimental work that may be used to validate and refine the model presented here.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1016/j.bpj.2026.08.001

Authors

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Institution:
University of Oxford
Division:
MPLS
Department:
Mathematical Institute
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MPLS
Department:
Mathematical Institute
Role:
Author
ORCID:
0000-0002-6304-9333
More by this author
Institution:
University of Oxford
Division:
MPLS
Department:
Mathematical Institute
Role:
Author


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Funder identifier:
https://ror.org/01cmst727
Grant:
MP-SIP-00001828
More from this funder
Funder identifier:
https://ror.org/00cwqg982
Grant:
BB/T008784/1


Publisher:
Cell Press
Journal:
Biophysical Journal More from this journal
Publication date:
2026-08-07
Acceptance date:
2026-07-14
DOI:
EISSN:
1542-0086
ISSN:
0006-3495


Language:
English
Pubs id:
2447738
Local pid:
pubs:2447738
Deposit date:
2026-07-31
ARK identifier:

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