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Extracellular matrix sensing via modulation of orientational order of integrins and F-actin in focal adhesions

Grudtsyna, Valeriia LU ; Packirisamy, Swathi LU orcid ; Bidone, Tamara C. and Swaminathan, Vinay LU (2023) In Life Science Alliance 6(10).
Abstract

Specificity of cellular responses to distinct cues from the ECM requires precise and sensitive decoding of physical information. However, how known mechanisms of mechanosensing like force-dependent catch bonds and conformational changes in FA proteins can confer that this sensitivity is not known. Using polarization microscopy and computational modeling, we identify dynamic changes in an orientational order of FA proteins as a molecular organizational mechanism that can fine-tune cell sensitivity to the ECM. We find that αV integrins and F-actin show precise changes in the orientational order in an ECM-mediated integrin activation-dependent manner. These changes are sensitive to ECM density and are regulated independent of myosin-II... (More)

Specificity of cellular responses to distinct cues from the ECM requires precise and sensitive decoding of physical information. However, how known mechanisms of mechanosensing like force-dependent catch bonds and conformational changes in FA proteins can confer that this sensitivity is not known. Using polarization microscopy and computational modeling, we identify dynamic changes in an orientational order of FA proteins as a molecular organizational mechanism that can fine-tune cell sensitivity to the ECM. We find that αV integrins and F-actin show precise changes in the orientational order in an ECM-mediated integrin activation-dependent manner. These changes are sensitive to ECM density and are regulated independent of myosin-II activity though contractility can enhance this sensitivity. A molecular-clutch model demonstrates that the orientational order of integrin-ECM binding coupled to directional catch bonds can capture cellular responses to changes in ECM density. This mechanism also captures decoupling of ECM density sensing from stiffness sensing thus elucidating specificity. Taken together, our results suggest relative geometric organization of FA molecules as an important molecular architectural feature and regulator of mechanotransduction.

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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Life Science Alliance
volume
6
issue
10
publisher
Rockefeller University Press
external identifiers
  • pmid:37463754
  • scopus:85165520943
ISSN
2575-1077
DOI
10.26508/lsa.202301898
language
English
LU publication?
yes
id
d34a1de6-def2-4494-8d91-e146f31045a6
date added to LUP
2023-08-25 14:25:15
date last changed
2024-04-20 01:52:20
@article{d34a1de6-def2-4494-8d91-e146f31045a6,
  abstract     = {{<p>Specificity of cellular responses to distinct cues from the ECM requires precise and sensitive decoding of physical information. However, how known mechanisms of mechanosensing like force-dependent catch bonds and conformational changes in FA proteins can confer that this sensitivity is not known. Using polarization microscopy and computational modeling, we identify dynamic changes in an orientational order of FA proteins as a molecular organizational mechanism that can fine-tune cell sensitivity to the ECM. We find that αV integrins and F-actin show precise changes in the orientational order in an ECM-mediated integrin activation-dependent manner. These changes are sensitive to ECM density and are regulated independent of myosin-II activity though contractility can enhance this sensitivity. A molecular-clutch model demonstrates that the orientational order of integrin-ECM binding coupled to directional catch bonds can capture cellular responses to changes in ECM density. This mechanism also captures decoupling of ECM density sensing from stiffness sensing thus elucidating specificity. Taken together, our results suggest relative geometric organization of FA molecules as an important molecular architectural feature and regulator of mechanotransduction.</p>}},
  author       = {{Grudtsyna, Valeriia and Packirisamy, Swathi and Bidone, Tamara C. and Swaminathan, Vinay}},
  issn         = {{2575-1077}},
  language     = {{eng}},
  number       = {{10}},
  publisher    = {{Rockefeller University Press}},
  series       = {{Life Science Alliance}},
  title        = {{Extracellular matrix sensing via modulation of orientational order of integrins and F-actin in focal adhesions}},
  url          = {{http://dx.doi.org/10.26508/lsa.202301898}},
  doi          = {{10.26508/lsa.202301898}},
  volume       = {{6}},
  year         = {{2023}},
}