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Stabilization of adhesions controls F-actin architecture in mechanotransduction

Carney, Keith R. ; Sondaz, Remi ; Sturgess, Wesley LU ; Sakthivel, Kabilan LU orcid ; Kim, Jungkyu ; Swaminathan, Vinay LU orcid and Bidone, Tamara C. (2025) In Communications Materials 6(1).
Abstract

A cell’s ability to sense and respond to the mechanical properties of the extracellular matrix (ECM) is essential for maintaining tissue homeostasis, and its disruption contributes to diseases such as fibrosis, cardiovascular disorders, and cancer. Effective mechanical coupling between the plasma membrane, the underlying filamentous actin (F-actin) cytoskeleton, and integrin-based adhesion complexes (IACs) is required to link ECM mechanics to cell morphology, yet the underlying mechanisms remain incompletely understood. Here, we combine computational modeling and high-resolution imaging to show that integrin–ECM bonds determine F-actin cytoskeleton organization. On soft substrates, short-lived IACs bonds allow rapid actin retrograde... (More)

A cell’s ability to sense and respond to the mechanical properties of the extracellular matrix (ECM) is essential for maintaining tissue homeostasis, and its disruption contributes to diseases such as fibrosis, cardiovascular disorders, and cancer. Effective mechanical coupling between the plasma membrane, the underlying filamentous actin (F-actin) cytoskeleton, and integrin-based adhesion complexes (IACs) is required to link ECM mechanics to cell morphology, yet the underlying mechanisms remain incompletely understood. Here, we combine computational modeling and high-resolution imaging to show that integrin–ECM bonds determine F-actin cytoskeleton organization. On soft substrates, short-lived IACs bonds allow rapid actin retrograde flow and dense branching, restricting protrusion and limiting cell spreading. In contrast, stiff substrates or Mn²⁺-mediated integrin activation stabilize adhesions, promote filament alignment, and drive membrane protrusion for cell spreading. These cytoskeletal transitions arise from feedback between adhesion strength and the spatial positioning of the F-actin barbed ends relative to the leading-edge membrane. This positioning determines whether filaments polymerize into linear bundles or branch into dendritic networks, each generating distinct protrusive forces that regulate cell spreading. Collectively, our findings establish integrin–ECM bond stability as a key regulator of F-actin cytoskeleton organization and cell morphology.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Communications Materials
volume
6
issue
1
article number
288
publisher
Springer Nature
external identifiers
  • scopus:105025689551
  • pmid:41458455
DOI
10.1038/s43246-025-01006-8
language
English
LU publication?
yes
id
1e2658d7-fa5b-4178-b1cc-df7bfd4d3c32
date added to LUP
2026-02-12 10:46:25
date last changed
2026-02-13 03:43:19
@article{1e2658d7-fa5b-4178-b1cc-df7bfd4d3c32,
  abstract     = {{<p>A cell’s ability to sense and respond to the mechanical properties of the extracellular matrix (ECM) is essential for maintaining tissue homeostasis, and its disruption contributes to diseases such as fibrosis, cardiovascular disorders, and cancer. Effective mechanical coupling between the plasma membrane, the underlying filamentous actin (F-actin) cytoskeleton, and integrin-based adhesion complexes (IACs) is required to link ECM mechanics to cell morphology, yet the underlying mechanisms remain incompletely understood. Here, we combine computational modeling and high-resolution imaging to show that integrin–ECM bonds determine F-actin cytoskeleton organization. On soft substrates, short-lived IACs bonds allow rapid actin retrograde flow and dense branching, restricting protrusion and limiting cell spreading. In contrast, stiff substrates or Mn²⁺-mediated integrin activation stabilize adhesions, promote filament alignment, and drive membrane protrusion for cell spreading. These cytoskeletal transitions arise from feedback between adhesion strength and the spatial positioning of the F-actin barbed ends relative to the leading-edge membrane. This positioning determines whether filaments polymerize into linear bundles or branch into dendritic networks, each generating distinct protrusive forces that regulate cell spreading. Collectively, our findings establish integrin–ECM bond stability as a key regulator of F-actin cytoskeleton organization and cell morphology.</p>}},
  author       = {{Carney, Keith R. and Sondaz, Remi and Sturgess, Wesley and Sakthivel, Kabilan and Kim, Jungkyu and Swaminathan, Vinay and Bidone, Tamara C.}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Springer Nature}},
  series       = {{Communications Materials}},
  title        = {{Stabilization of adhesions controls F-actin architecture in mechanotransduction}},
  url          = {{http://dx.doi.org/10.1038/s43246-025-01006-8}},
  doi          = {{10.1038/s43246-025-01006-8}},
  volume       = {{6}},
  year         = {{2025}},
}