TY - JOUR
T1 - Initiation of fibronectin fibrillogenesis is an enzyme-dependent process
AU - Melamed, Shay
AU - Zaffryar-Eilot, Shelly
AU - Nadjar-Boger, Elisabeth
AU - Aviram, Rohtem
AU - Zhao, Huaning
AU - Yaseen-Badarne, Wesal
AU - Kalev-Altman, Rotem
AU - Sela-Donenfeld, Dalit
AU - Lewinson, Oded
AU - Astrof, Sophie
AU - Hasson, Peleg
AU - Wolfenson, Haguy
N1 - Publisher Copyright:
© 2023
PY - 2023/5/30
Y1 - 2023/5/30
N2 - Fibronectin fibrillogenesis and mechanosensing both depend on integrin-mediated force transmission to the extracellular matrix. However, force transmission is in itself dependent on fibrillogenesis, and fibronectin fibrils are found in soft embryos where high forces cannot be applied, suggesting that force cannot be the sole initiator of fibrillogenesis. Here, we identify a nucleation step prior to force transmission, driven by fibronectin oxidation mediated by lysyl oxidase enzyme family members. This oxidation induces fibronectin clustering, which promotes early adhesion, alters cellular response to soft matrices, and enhances force transmission to the matrix. In contrast, absence of fibronectin oxidation abrogates fibrillogenesis, perturbs cell-matrix adhesion, and compromises mechanosensation. Moreover, fibronectin oxidation promotes cancer cell colony formation in soft agar as well as collective and single-cell migration. These results reveal a force-independent enzyme-dependent mechanism that initiates fibronectin fibrillogenesis, establishing a critical step in cell adhesion and mechanosensing.
AB - Fibronectin fibrillogenesis and mechanosensing both depend on integrin-mediated force transmission to the extracellular matrix. However, force transmission is in itself dependent on fibrillogenesis, and fibronectin fibrils are found in soft embryos where high forces cannot be applied, suggesting that force cannot be the sole initiator of fibrillogenesis. Here, we identify a nucleation step prior to force transmission, driven by fibronectin oxidation mediated by lysyl oxidase enzyme family members. This oxidation induces fibronectin clustering, which promotes early adhesion, alters cellular response to soft matrices, and enhances force transmission to the matrix. In contrast, absence of fibronectin oxidation abrogates fibrillogenesis, perturbs cell-matrix adhesion, and compromises mechanosensation. Moreover, fibronectin oxidation promotes cancer cell colony formation in soft agar as well as collective and single-cell migration. These results reveal a force-independent enzyme-dependent mechanism that initiates fibronectin fibrillogenesis, establishing a critical step in cell adhesion and mechanosensing.
KW - CP: Cell biology
KW - cell adhesion
KW - fibronectin fibrillogenesis
KW - lysyl oxidaze family
KW - mechanosensing
UR - http://www.scopus.com/inward/record.url?scp=85156167896&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2023.112473
DO - 10.1016/j.celrep.2023.112473
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C2 - 37148241
AN - SCOPUS:85156167896
SN - 2211-1247
VL - 42
JO - Cell Reports
JF - Cell Reports
IS - 5
M1 - 112473
ER -
