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
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.
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.
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 |
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 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.
Publications since 2017
Review since 2017
Book chapter since 2017
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.
Michel Labouesse – IBPS
Benoît Ladoux / René-Marc Mège – IJM
Jean-Baptiste Manneville – MSC
Stefano Marullo – Institut Cochin
Matthieu Piel – IPGG
Vanessa Ribes – IJM
Fondation ARC pour la recherche sur le cancer
Agence Nationale de la Recherche (ANR)
Labex Who Am I?
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