Institut Jacques Monod
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Mechanotransduction: from Cell Surface to Nucleus

NICOLAS BORGHI

How our cells respond to their mechanical environment?

We propose an approach using quantitative fluorescence microscopy and genetic engineering for responses from the molecule to the tissue.

Keywords: mechanotransduction, cell adhesion, cell migration, microscopy, biosensors, biophysics

+33 (0)157278041     nicolas.borghi(at)ijm.fr

Research

In multicellular organisms, cells generate and undergo mechanical forces that propagate throughout the organism. These forces can determine the shape of tissues and organs, and regulate genetic programs. However, the molecular mechanisms of the transmission of mechanical forces and their transduction into biochemical signals are poorly understood.

Our project focuses on the macromolecular complexes that transmit and transduce these mechanical signals within and between cells, and the cellular functions that depend on them. We are interested in plasma membrane adhesion receptors, nuclear envelope transmembrane complexes and their functions in cell adhesion, migration, proliferation and transcriptional activity.

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To address this goal, we develop and use genetically encoded biosensors and advanced microscopy and micromanipulation methods on cell culture model systems. This combination allows us to dynamically and quantitatively control and measure the behavior of protein complexes and cells in a wide range of time and length scales.

 

Members

Group Leader:

Nicolas BORGHI
Téléphone : +33 (0)157278041
nicolas.borghi [at] ijm.fr

 

Members:

Nicolas AUDUGE Photonic microscopy engineer
Maïté COPPEY-MOISAN Emeritus Researcher
Philippe GIRARD Lecturer-researcher
Louis LAURENT PhD Student
Thomas GERMIER Postdoc
Hugo LACHUER Postdoc
Mariia BALATSKAIA Postdoc
Thanusthika THAYATHARAN intern
Tugba AGYAR intern

Selected Publications

1: Déjardin T, Carollo PS, Sipieter F, Davidson PM, Seiler C, Cuvelier D, Cadot, B, Sykes C, Gomes ER, Borghi N. Nesprins are mechanotransducers that discriminate epithelial-mesenchymal transition programs. J Cell Biol. 2020 Oct 5;219(10):e201908036. doi: 10.1083/jcb.201908036. PMID: 32790861; PMCID: PMC7659719.

2: Davidson PM, Battistella A, Déjardin T, Betz T, Plastino J, Borghi N, Cadot, B, Sykes C. Nesprin-2 accumulates at the front of the nucleus during confined. cell migration. EMBO Rep. 2020 Jul 3;21(7):e49910. doi: 10.15252/embr.201949910. Epub 2020 May 17. PMID: 32419336; PMCID: PMC7332974.

3: Audugé N, Padilla-Parra S, Tramier M, Borghi N, Coppey-Moisan M. Chromatin condensation fluctuations rather than steady-state predict chromatin accessibility. Nucleic Acids Res. 2019 Jul 9;47(12):6184-6194. doi: 10.1093/nar/gkz373. PMID: 31081027; PMCID: PMC6614833.

4: De Pascalis C, Pérez-González C, Seetharaman S, Boëda B, Vianay B, Burute M, Leduc C, Borghi N, Trepat X, Etienne-Manneville S. Intermediate filaments control collective migration by restricting traction forces and sustaining cell-cell contacts. J Cell Biol. 2018 Sep 3;217(9):3031-3044. doi: 10.1083/jcb.201801162. Epub 2018 Jul 6. PMID: 29980627; PMCID: PMC6122997.

5: Gayrard C, Bernaudin C, Déjardin T, Seiler C, Borghi N. Src- and confinement- dependent FAK activation causes E-cadherin relaxation and β-catenin activity. J Cell Biol. 2018 Mar 5;217(3):1063-1077. doi: 10.1083/jcb.201706013. Epub 2018 Jan 8. PMID: 29311227; PMCID: PMC5839785.

6: Sarangi BR, Gupta M, Doss BL, Tissot N, Lam F, Mège RM, Borghi N, Ladoux B. Coordination between Intra- and Extracellular Forces Regulates Focal Adhesion. Dynamics. Nano Lett. 2017 Jan 11;17(1):399-406. doi: 10.1021/acs.nanolett.6b04364. Epub 2016 Dec 23. PMID: 27990827; PMCID: PMC5423523.

7: Liu Z, Bun P, Audugé N, Coppey-Moisan M, Borghi N. Vinculin head-tail interaction defines multiple early mechanisms for cell substrate rigidity sensing. Integr Biol (Camb). 2016 Jun 13;8(6):693-703. doi: 10.1039/c5ib00307e. Epub 2016 May 11. PMID: 27169142.

8: Lowndes M, Rakshit S, Shafraz O, Borghi N, Harmon RM, Green KJ, Sivasankar S, Nelson WJ. Different roles of cadherins in the assembly and structural integrity of the desmosome complex. J Cell Sci. 2014 May 15;127(Pt 10):2339-50. doi: 10.1242/jcs.146316. Epub 2014 Mar 7. PMID: 24610950; PMCID: PMC4021477.

9: Borghi N, Sorokina M, Shcherbakova OG, Weis WI, Pruitt BL, Nelson WJ, and Alexander R. Dunn. E-cadherin is under constitutive actomyosin-generated tension that is increased at cell-cell contacts upon externally applied stretch. Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12568-73. doi: 10.1073/pnas.1204390109. Epub 2012 Jul 16. Erratum in: Proc Natl Acad Sci U S A. 2012 Nov 13;109(46):19034. PMID: 22802638; PMCID: PMC3411997.

10: Borghi N, Lowndes M, Maruthamuthu V, Gardel ML, Nelson WJ. Regulation of cell motile behavior by crosstalk between cadherin- and integrin-mediated adhesions. Proc Natl Acad Sci U S A. 2010 Jul 27;107(30):13324-9. doi: 10.1073/pnas.1002662107. Epub 2010 Jun 21. PMID: 20566866; PMCID: PMC2922157.

All the publications

Publications since 2017

Donker, L., Houtekamer, R., Vliem, M., Sipieter, F., Canever, H., Gómez-González, M., Bosch-Padrós, M., Pannekoek, W.-J., Trepat, X., Borghi, N., & Gloerich, M. (2022). A mechanical G2 checkpoint controls epithelial cell division through E-cadherin-mediated regulation of Wee1-Cdk1. Cell Reports, 41(2), 111475. https://doi.org/10.1016/j.celrep.2022.111475
Sipieter, F., Laurent, L., Girard, P. P., & Borghi, N. (2022). Molecular tension microscopy of the LINC complex in live cells. STAR Protocols, 3(3), 101538. https://doi.org/10.1016/j.xpro.2022.101538
Leroy, O., van Leen, E., Girard, P., Villedieu, A., Hubert, C., Bosveld, F., Bellaïche, Y., & Renaud, O. (2022). Multi-view confocal microscopy enables multiple organ and whole organism live-imaging. Development (Cambridge, England), 149(4), dev199760. https://doi.org/10.1242/dev.199760
Sipieter, F., Laurent, L., & Borghi, N. (2021). Nesprins mechanically discriminate between distinct epithelium-to-mesenchyme transitions. Medecine Sciences: M/S, 37(11), 984–986. https://doi.org/10.1051/medsci/2021132
Roebroek, T., Vandenberg, W., Sipieter, F., Hugelier, S., Stove, C., Zhang, J., & Dedecker, P. (2021). Simultaneous readout of multiple FRET pairs using photochromism. Nature Communications, 12(1), 2005. https://doi.org/10.1038/s41467-021-22043-0
Atlas, Y., Gorin, C., Novais, A., Marchand, M. F., Chatzopoulou, E., Lesieur, J., Bascetin, R., Binet-Moussy, C., Sadoine, J., Lesage, M., Opsal-Vital, S., Péault, B., Monnot, C., Poliard, A., Girard, P., Germain, S., Chaussain, C., & Muller, L. (2021). Microvascular maturation by mesenchymal stem cells in vitro improves blood perfusion in implanted tissue constructs. Biomaterials, 268, 120594. https://doi.org/10.1016/j.biomaterials.2020.120594
Aladin, D. M. K., Chu, Y. S., Shen, S., Robinson, R. C., Dufour, S., Viasnoff, V., Borghi, N., & Thiery, J. P. (2021). Extracellular domains of E-cadherin determine key mechanical phenotypes of an epithelium through cell- and non-cell-autonomous outside-in signaling. PloS One, 16(12), e0260593. https://doi.org/10.1371/journal.pone.0260593
Déjardin, T., Carollo, P. S., Sipieter, F., Davidson, P. M., Seiler, C., Cuvelier, D., Cadot, B., Sykes, C., Gomes, E. R., & Borghi, N. (2020). Nesprins are mechanotransducers that discriminate epithelial-mesenchymal transition programs. The Journal of Cell Biology, 219(10), e201908036. https://doi.org/10.1083/jcb.201908036
Davidson, P. M., Battistella, A., Déjardin, T., Betz, T., Plastino, J., Borghi, N., Cadot, B., & Sykes, C. (2020). Nesprin-2 accumulates at the front of the nucleus during confined cell migration. EMBO Reports, 21(7), e49910. https://doi.org/10.15252/embr.201949910
Umana-Diaz, C., Pichol-Thievend, C., Marchand, M. F., Atlas, Y., Salza, R., Malbouyres, M., Barret, A., Teillon, J., Ardidie-Robouant, C., Ruggiero, F., Monnot, C., Girard, P., Guilluy, C., Ricard-Blum, S., Germain, S., & Muller, L. (2020). Scavenger Receptor Cysteine-Rich domains of Lysyl Oxidase-Like2 regulate endothelial ECM and angiogenesis through non-catalytic scaffolding mechanisms. Matrix Biology: Journal of the International Society for Matrix Biology, 88, 33–52. https://doi.org/10.1016/j.matbio.2019.11.003
Audugé, N., Padilla-Parra, S., Tramier, M., Borghi, N., & Coppey-Moisan, M. (2019). Chromatin condensation fluctuations rather than steady-state predict chromatin accessibility. Nucleic Acids Research, 47(12), 6184–6194. https://doi.org/10.1093/nar/gkz373
De Pascalis, C., Pérez-González, C., Seetharaman, S., Boëda, B., Vianay, B., Burute, M., Leduc, C., Borghi, N., Trepat, X., & Etienne-Manneville, S. (2018). Intermediate filaments control collective migration by restricting traction forces and sustaining cell-cell contacts. The Journal of Cell Biology, 217(9), 3031–3044. https://doi.org/10.1083/jcb.201801162
Gayrard, C., & Borghi, N. (2018). How mechanotransduction between adhesion complexes results in β-catenin pathway activation. Medecine Sciences: M/S, 34(6–7), 506–508. https://doi.org/10.1051/medsci/20183406004
Gayrard, C., Bernaudin, C., Déjardin, T., Seiler, C., & Borghi, N. (2018). Src- and confinement-dependent FAK activation causes E-cadherin relaxation and β-catenin activity. The Journal of Cell Biology, 217(3), 1063–1077. https://doi.org/10.1083/jcb.201706013
Sarangi, B. R., Gupta, M., Doss, B. L., Tissot, N., Lam, F., Mège, R.-M., Borghi, N., & Ladoux, B. (2017). Coordination between Intra- and Extracellular Forces Regulates Focal Adhesion Dynamics. Nano Letters, 17(1), 399–406. https://doi.org/10.1021/acs.nanolett.6b04364

 

Review since 2017

Canever, H., Sipieter, F., & Borghi, N. (2020). When Separation Strengthens Ties. Trends in Cell Biology, 30(3), 169–170. https://doi.org/10.1016/j.tcb.2019.12.002

 

Book chapter since 2017

Canever, H., Carollo, P. S., Fleurisson, R., Girard, P. P., & Borghi, N. (2021). Molecular Tension Microscopy of E-Cadherin During Epithelial-Mesenchymal Transition. Methods in Molecular Biology (Clifton, N.J.), 2179, 289–299. https://doi.org/10.1007/978-1-0716-0779-4_22

Theses

2017: Charlène Gayrard – Mécanotransduction au complexe E-cadhérine/bêta-caténine lors de la transition épithélio-mésenchymateuse.
2019: Pietro Salvatore Carollo – The LINC complex is a mechanotransducer that regulates catenin signalling dyring epithelial-mesenchymal transitions.
2021: Helena Canever – Regulation of epithelial migration by cell adhesions: roles of vinculin.
Ongoing: Louis Laurent.

Collaborations

Michel Labouesse – IBPS
Benoît Ladoux / René-Marc Mège – IJM
Jean-Baptiste Manneville – MSC
Stefano Marullo – Institut Cochin
Matthieu Piel – IPGG
Vanessa Ribes – IJM

GRANTS – FUNDING

Fondation ARC pour la recherche sur le cancer
Agence Nationale de la Recherche (ANR)
Labex Who Am I?

News

– Check this preprint out of a great collaboration with the Gloerich and Trepat labs: https://doi.org/10.1101/2021.11.29.470352

– We’re hiring! check below.