Extracellular matrix sensing via modulation of orientational order of integrins and F-actin in focal adhesions
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
Extracellular matrix sensing via modulation of orientational order of integrins and F-actin in focal adhesions. / Grudtsyna, Valeriia; Packirisamy, Swathi; Bidone, Tamara C.; Swaminathan, Vinay.
I: Life Science Alliance, Bind 6, Nr. 10, e202301898, 10.08.2023.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Extracellular matrix sensing via modulation of orientational order of integrins and F-actin in focal adhesions
AU - Grudtsyna, Valeriia
AU - Packirisamy, Swathi
AU - Bidone, Tamara C.
AU - Swaminathan, Vinay
N1 - Publisher Copyright: © 2023 Grudtsyna et al.
PY - 2023/8/10
Y1 - 2023/8/10
N2 - 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.
AB - 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.
U2 - 10.26508/lsa.202301898
DO - 10.26508/lsa.202301898
M3 - Journal article
C2 - 37463754
AN - SCOPUS:85165520943
VL - 6
JO - Life Science Alliance
JF - Life Science Alliance
SN - 2575-1077
IS - 10
M1 - e202301898
ER -
ID: 361685348