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

Recherche

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.

Membres

Responsable :

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

Membres de l’équipe :

Nicolas	AUDUGE	Ingénieur en microscopie photonique
Maïté	COPPEY	Chercheur émérite
Philippe	GIRARD	Enseignant-chercheur
Louis	LAURENT	Doctorant
Thomas	GERMIER	Post-doctorant
Hugo	LACHUER	Post-doctorant
Mariia	BALATSKAIA	Post-doctorante

Sélection de 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.

Toutes les publications depuis 2017

Publications

Cicero, J., Trouvilliez, S., Palma, M., Ternier, G., Decoster, L., Happernegg, E., Barois, N., Van Outryve, A., Dehouck, L., Bourette, R. P., Adriaenssens, E., Lagadec, C., Tarhan, C. M., Collard, D., Souguir, Z., Vandenhaute, E., Maubon, G., Sipieter, F., Borghi, N., … Toillon, R.-A. (2023). ProNGF promotes brain metastasis through TrkA/EphA2 induced Src activation in triple negative breast cancer cells. Experimental Hematology & Oncology, 12(1), 104. https://doi.org/10.1186/s40164-023-00463-6

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

Revue

Chapitre de livre

Thèses

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.