Initiation of fibronectin fibrillogenesis is an enzyme-dependent process

Shay Melamed; Shelly Zaffryar-Eilot; Elisabeth Nadjar-Boger; Rohtem Aviram; Huaning Zhao; Wesal Yaseen-Badarne; Rotem Kalev-Altman; Dalit Sela-Donenfeld; Oded Lewinson; Sophie Astrof; Peleg Hasson; Haguy Wolfenson

doi:10.1016/j.celrep.2023.112473

Initiation of fibronectin fibrillogenesis is an enzyme-dependent process

Shay Melamed, Shelly Zaffryar-Eilot, Elisabeth Nadjar-Boger, Rohtem Aviram, Huaning Zhao, Wesal Yaseen-Badarne, Rotem Kalev-Altman, Dalit Sela-Donenfeld, Oded Lewinson, Sophie Astrof, Peleg Hasson^*, Haguy Wolfenson^*

^*Corresponding author for this work

The Koret School of Veterinary Medicine

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

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.

Original language	American English
Article number	112473
Journal	Cell Reports
Volume	42
Issue number	5
DOIs	https://doi.org/10.1016/j.celrep.2023.112473
State	Published - 30 May 2023

Bibliographical note

Funding Information:
We would like to thank Mike Sheetz, Tom Schultheiss, and Ella Preger-Ben Noon for critical reading and helpful discussions. We would like to thank Maya Holdengreber from the Technion Biomedical Core Facility unit for assistance with the dSTORM imaging. We would like to thank Keren Bendalak from the Technion Proteomics Center for assistance with the MS experiments and analyses. H.W. is an incumbent of the David and Inez Myers Career Advancement Chair in Life Sciences. This research was supported by Israel Science Foundation grant 1738/17 (H.W.), Israel Science Foundation grant 111/18 (P.H.), Rappaport Family Foundation (H.W. and P.H.), and National Heart, Lung, and Blood Institute grants R01 HL103920, R01 HL134935, and R01 HL158049 (S.A.). S.M. designed the experiments and methodology, performed the experiments, analyzed the data, and wrote the manuscript. S.Z.-E. E.N.-B. R.A. H.Z. W.Y.-B. and R.K.-A. performed the experiments. D.S.-D. O.L. and S.A. supervised the performed experiments and assisted in conceptualization of the study. H.W. and P.H. were responsible for conceptualization, supervision, funding acquisition, and reviewing, writing, and editing the manuscript. The authors declare no competing interests. We support inclusive, diverse, and equitable conduct of research.

Funding Information:
We would like to thank Mike Sheetz, Tom Schultheiss, and Ella Preger-Ben Noon for critical reading and helpful discussions. We would like to thank Maya Holdengreber from the Technion Biomedical Core Facility unit for assistance with the dSTORM imaging. We would like to thank Keren Bendalak from the Technion Proteomics Center for assistance with the MS experiments and analyses. H.W. is an incumbent of the David and Inez Myers Career Advancement Chair in Life Sciences. This research was supported by Israel Science Foundation grant 1738/17 (H.W.), Israel Science Foundation grant 111/18 (P.H.), Rappaport Family Foundation (H.W. and P.H.), and National Heart, Lung, and Blood Institute grants R01 HL103920 , R01 HL134935 , and R01 HL158049 (S.A.).

Publisher Copyright:
© 2023

Keywords

CP: Cell biology
cell adhesion
fibronectin fibrillogenesis
lysyl oxidaze family
mechanosensing

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.celrep.2023.112473

Cite this

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title = "Initiation of fibronectin fibrillogenesis is an enzyme-dependent process",

abstract = "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.",

keywords = "CP: Cell biology, cell adhesion, fibronectin fibrillogenesis, lysyl oxidaze family, mechanosensing",

author = "Shay Melamed and Shelly Zaffryar-Eilot and Elisabeth Nadjar-Boger and Rohtem Aviram and Huaning Zhao and Wesal Yaseen-Badarne and Rotem Kalev-Altman and Dalit Sela-Donenfeld and Oded Lewinson and Sophie Astrof and Peleg Hasson and Haguy Wolfenson",

note = "Funding Information: We would like to thank Mike Sheetz, Tom Schultheiss, and Ella Preger-Ben Noon for critical reading and helpful discussions. We would like to thank Maya Holdengreber from the Technion Biomedical Core Facility unit for assistance with the dSTORM imaging. We would like to thank Keren Bendalak from the Technion Proteomics Center for assistance with the MS experiments and analyses. H.W. is an incumbent of the David and Inez Myers Career Advancement Chair in Life Sciences. This research was supported by Israel Science Foundation grant 1738/17 (H.W.), Israel Science Foundation grant 111/18 (P.H.), Rappaport Family Foundation (H.W. and P.H.), and National Heart, Lung, and Blood Institute grants R01 HL103920, R01 HL134935, and R01 HL158049 (S.A.). S.M. designed the experiments and methodology, performed the experiments, analyzed the data, and wrote the manuscript. S.Z.-E. E.N.-B. R.A. H.Z. W.Y.-B. and R.K.-A. performed the experiments. D.S.-D. O.L. and S.A. supervised the performed experiments and assisted in conceptualization of the study. H.W. and P.H. were responsible for conceptualization, supervision, funding acquisition, and reviewing, writing, and editing the manuscript. The authors declare no competing interests. We support inclusive, diverse, and equitable conduct of research. Funding Information: We would like to thank Mike Sheetz, Tom Schultheiss, and Ella Preger-Ben Noon for critical reading and helpful discussions. We would like to thank Maya Holdengreber from the Technion Biomedical Core Facility unit for assistance with the dSTORM imaging. We would like to thank Keren Bendalak from the Technion Proteomics Center for assistance with the MS experiments and analyses. H.W. is an incumbent of the David and Inez Myers Career Advancement Chair in Life Sciences. This research was supported by Israel Science Foundation grant 1738/17 (H.W.), Israel Science Foundation grant 111/18 (P.H.), Rappaport Family Foundation (H.W. and P.H.), and National Heart, Lung, and Blood Institute grants R01 HL103920 , R01 HL134935 , and R01 HL158049 (S.A.). Publisher Copyright: {\textcopyright} 2023",

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doi = "10.1016/j.celrep.2023.112473",

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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 - Funding Information: We would like to thank Mike Sheetz, Tom Schultheiss, and Ella Preger-Ben Noon for critical reading and helpful discussions. We would like to thank Maya Holdengreber from the Technion Biomedical Core Facility unit for assistance with the dSTORM imaging. We would like to thank Keren Bendalak from the Technion Proteomics Center for assistance with the MS experiments and analyses. H.W. is an incumbent of the David and Inez Myers Career Advancement Chair in Life Sciences. This research was supported by Israel Science Foundation grant 1738/17 (H.W.), Israel Science Foundation grant 111/18 (P.H.), Rappaport Family Foundation (H.W. and P.H.), and National Heart, Lung, and Blood Institute grants R01 HL103920, R01 HL134935, and R01 HL158049 (S.A.). S.M. designed the experiments and methodology, performed the experiments, analyzed the data, and wrote the manuscript. S.Z.-E. E.N.-B. R.A. H.Z. W.Y.-B. and R.K.-A. performed the experiments. D.S.-D. O.L. and S.A. supervised the performed experiments and assisted in conceptualization of the study. H.W. and P.H. were responsible for conceptualization, supervision, funding acquisition, and reviewing, writing, and editing the manuscript. The authors declare no competing interests. We support inclusive, diverse, and equitable conduct of research. Funding Information: We would like to thank Mike Sheetz, Tom Schultheiss, and Ella Preger-Ben Noon for critical reading and helpful discussions. We would like to thank Maya Holdengreber from the Technion Biomedical Core Facility unit for assistance with the dSTORM imaging. We would like to thank Keren Bendalak from the Technion Proteomics Center for assistance with the MS experiments and analyses. H.W. is an incumbent of the David and Inez Myers Career Advancement Chair in Life Sciences. This research was supported by Israel Science Foundation grant 1738/17 (H.W.), Israel Science Foundation grant 111/18 (P.H.), Rappaport Family Foundation (H.W. and P.H.), and National Heart, Lung, and Blood Institute grants R01 HL103920 , R01 HL134935 , and R01 HL158049 (S.A.). 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

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U2 - 10.1016/j.celrep.2023.112473

DO - 10.1016/j.celrep.2023.112473

M3 - Article

C2 - 37148241

AN - SCOPUS:85156167896

SN - 2211-1247

VL - 42

JO - Cell Reports

JF - Cell Reports

IS - 5

M1 - 112473

ER -

Initiation of fibronectin fibrillogenesis is an enzyme-dependent process

Abstract

Bibliographical note

Keywords

UN SDGs

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