Mécanotransduction : de la surface de la cellule à son noyau

NICOLAS BORGHI

Notre équipe étudie comment nos cellules réagissent à leur environnement mécanique. Nous proposons une approche par microscopies de fluorescence quantitatives et ingénierie génétique pour des réponses de la molécule au tissu.

Mots-clés : mécanotransduction, adhésion cellulaire, migration cellulaire, microscopie, biosenseurs, biophysique 

 

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

Dans les organismes multicellulaires, les cellules génèrent et subissent des forces mécaniques qui se propagent dans tout l’organisme. Ces forces peuvent déterminer la forme des tissus et organes, et réguler des programmes génétiques. Les mécanismes moléculaires de la transmission des forces mécaniques et de leur transduction en signaux biochimiques sont cependant mal connus.

Notre projet porte sur les complexes macromoléculaires qui transmettent et transduisent ces signaux mécaniques à l’intérieur et entre les cellules, et les fonctions cellulaires qui en dépendent. Nous nous intéressons aux récepteurs d’adhésion de la membrane plasmique, aux complexes transmembranaires de l’enveloppe nucléaire et leurs fonctions dans l’adhésion cellulaire, la migration, la prolifération et l’activité transcriptionnelle.

Film 1

Pour répondre à cet objectif, nous développons et utilisons des biosenseurs génétiquement encodés et des méthodes de microscopie et de micromanipulation avancées sur des systèmes modèles de culture cellulaire. Cette combinaison permet de contrôler et mesurer dynamiquement et quantitativement le comportement des complexes de protéines et des cellules dans un large éventail d’échelles de temps et de longueur.

Responsable :

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

 

Membres de l’équipe :

Nicolas AUDUGE Ingénieur en microscopie photonique
Maïté COPPEY-MOISAN Chercheur émérite
Philippe GIRARD Enseignant-chercheur
Louis LAURENT Doctorant
François SIPIETER Postdoctorant

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.

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:

– We’re hiring! check below.