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.

 

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
François	SIPIETER	Postdoc

Leroy O, van Leen E, Girard P, Villedieu A, Hubert C, Bosveld F, Bellaïche Y, Renaud O.

Multi-view confocal microscopy enables multiple organ and whole organism live-imaging.

Development. 2022 Feb 15;149(4):dev199760. doi: 10.1242/dev.199760. Epub 2022 Feb 21. PMID: 35072204.

 

Aladin DMK, Chu YS, Shen S, Robinson RC, Dufour S, Viasnoff V, Borghi N, Thiery JP.

Extracellular domains of E-cadherin determine key mechanical phenotypes of an epithelium through cell- and non-cell-autonomous outside-in
signaling.

PLoS One. 2021 Dec 22;16(12):e0260593. doi: 10.1371/journal.pone.0260593. PMID: 34937057; PMCID: PMC8694416.

 

Sipieter F, Laurent L, Borghi N.

Les nesprines, des protéines de l’enveloppe nucléaire, contrôlent mécaniquement différentes transitions épithélio-mésenchymateuses [Nesprins mechanically discriminate between distinct epithelium-to-mesenchyme transitions].

Med Sci (Paris). 2021 Nov;37(11):984-986. French. doi: 10.1051/medsci/2021132. Epub 2021 Dec 1. PMID: 34851273.

 

Atlas Y, Gorin C, Novais A, Marchand MF, 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.

Microvascular maturation by mesenchymal stem cells in vitro improves blood perfusion in implanted tissue constructs.

Biomaterials. 2021 Jan;268:120594. doi: 10.1016/j.biomaterials.2020.120594. Epub 2020 Dec 19. PMID: 33387754.

 

Canever H, Carollo PS, Fleurisson R, Girard PP, Borghi N.

Molecular Tension Microscopy of E-Cadherin During Epithelial-Mesenchymal Transition.

Methods Mol Biol. 2021;2179:289-299. doi: 10.1007/978-1-0716-0779-4_22. PMID: 32939728.

 

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.

 

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.

 

Umana-Diaz C, Pichol-Thievend C, Marchand MF, 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.

Scavenger Receptor Cysteine-Rich domains of Lysyl Oxidase-Like2 regulate endothelial ECM and angiogenesis through non- catalytic scaffolding mechanisms.

Matrix Biol. 2020 Jun;88:33-52. doi: 10.1016/j.matbio.2019.11.003. Epub 2019 Nov 20. PMID: 31759052.

 

Canever H, Sipieter F, Borghi N.

When Separation Strengthens Ties.

Trends Cell Biol. 2020 Mar;30(3):169-170. doi: 10.1016/j.tcb.2019.12.002. Epub 2020 Jan. PMID: 31954602.

 

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.

 

Wang G, Nola S, Bovio S, Bun P, Coppey-Moisan M, Lafont F, Galli T.

Biomechanical Control of Lysosomal Secretion Via the VAMP7 Hub: A Tug-of-War between VARP and LRRK1.

iScience. 2018 Jun 29;4:127-143. doi: 10.1016/j.isci.2018.05.016. Epub 2018 May 29. PMID: 30240735; PMCID: PMC6147023.

 

Gayrard C, Borghi N.

Activation de la voie β-caténine par mécanotransduction entre complexes d’adhérence [How mechanotransduction between adhesion complexes results in β-catenin pathway activation].

Med Sci (Paris). 2018 Jun-Jul;34(6-7):506-508. French. doi: 10.1051/medsci/20183406004. Epub 2018 Jul 31. PMID: 30067197.

 

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.

 

Souquet B, Freed E, Berto A, Andric V, Audugé N, Reina-San-Martin B, Lacy E, Doye V.

Nup133 Is Required for Proper Nuclear Pore Basket Assembly and Dynamics in Embryonic Stem Cells.

Cell Rep. 2018 May 22;23(8):2443-2454. doi: 10.1016/j.celrep.2018.04.070. Erratum in: Cell Rep. 2018 Nov 13;25(7):1994. PMID: 29791854; PMCID: PMC5995580.

 

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.

 

Tissot N, Lepesant JA, Bernard F, Legent K, Bosveld F, Martin C, Faklaris O, Bellaïche Y, Coppey M, Guichet A.

Distinct molecular cues ensure a robust microtubule-dependent nuclear positioning in the Drosophila oocyte.

Nat Commun. 2017 Apr 27;8:15168. doi: 10.1038/ncomms15168. PMID: 28447612; PMCID: PMC5414183.

 

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.

 

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.

 

Borghi N, Farge E, Lavelle C.

Experimental approaches in mechanotransduction: From molecules to pathology.

Methods. 2016 Feb 1;94:1-3. doi: 10.1016/j.ymeth.2016.01.007. PMID: 26896045.

 

Gayrard C, Borghi N.

FRET-based Molecular Tension Microscopy.

Methods. 2016 Feb 1;94:33-42. doi: 10.1016/j.ymeth.2015.07.010. Epub 2015 Jul 22. PMID: 26210398.

 

Suzuki M, Sakata I, Sakai T, Tomioka H, Nishigaki K, Tramier M, Coppey-Moisan M

A high-throughput direct fluorescence resonance energy transfer-based assay for analyzing apoptotic proteases using flow cytometry and fluorescence lifetime measurements.

Anal Biochem. 2015 Dec 15;491:10-7. doi: 10.1016/j.ab.2015.08.022. Epub 2015 Sep 1. PMID: 26334608.

 

Padilla-Parra S, Audugé N, Tramier M, Coppey-Moisan M.

Time-domain fluorescence lifetime imaging microscopy: a quantitative method to follow transient protein-protein interactions in living cells.

Cold Spring Harb Protoc. 2015 Jun 1;2015(6):508-21. doi: 10.1101/pdb.top086249. PMID: 26034312.

 

Morchoisne-Bolhy S, Geoffroy MC, Bouhlel IB, Alves A, Audugé N, Baudin X, Van Bortle K, Powers MA, Doye V.

Intranuclear dynamics of the Nup107-160 complex.

Mol Biol Cell. 2015 Jun 15;26(12):2343-56. doi: 10.1091/mbc.E15-02-0060. Epub 2015 Apr 22. PMID: 25904327; PMCID: PMC4462950.

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?

– 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.

19/04/2022 – Two postdoctoral positions in Epithelial mechanotransduction