Mechanotransduction: from Cell Surface to Nucleus

Group leader

In multicellular organisms, cells generate and experience mechanical forces that are propagated throughout the organism. Ultimately, these forces may shape tissues and organs, and regulate genetic programs. The molecular mechanisms of mechanical force transmission and transduction into biochemical signals are, however, poorly understood.

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

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

This work is supported by The French National Research Agency and Fondation ARC pour la recherche sur le cancer, Fondation pour la Recherche Médicale, L’Oréal-UNESCO For Women in Science, INSPIRE USPC Horizon 2020, La Ligue contre le cancer, France BioImaging, China Scholarship council, Zeiss.

Selection of Publications

Nesprins are mechanotransducers that discriminate epithelial-mesenchymal transition programs.
Déjardin T, Carollo PS, Sipieter F, Davidson PM, Seiler C, Cuvelier D, Cadot B, Sykes C, Gomes ER, Borghi N.
The Journal of Cell Biology, (2020) 219:e201908036.
Spotlight in: J Cell Biol (2020) 219 (10): e202009042.

Nesprin-2 accumulates at the front of the nucleus during confined cell migration.
Davidson PM, Battistella A, Déjardin T, Betz T, Plastino J, Borghi N, Cadot B, Sykes C.
EMBO Reports, (2020) 21:e49910.

When Separation Strengthens Ties.
Canever H, Sipieter F, Borghi N.
Trends in Cell Biology, (2020) 30:169-170.

Chromatin condensation fluctuations rather than steady-state predict chromatin accessibility.
N. Audugé, S. Padilla-Parra, M. Tramier, N. Borghi, M. Coppey-Moisan.
Nucleic Acids Research, (2019) 47:6184-6194

Intermediate filaments control collective migration by restricting traction forces and sustaining cell-cell contacts.
C. De Pascalis, C. Pérez-González, S. Seetharaman, B. Boëda, B. Vianay, M. Burute M, C. Leduc, N. Borghi, X. Trepat, S. Etienne-Manneville.
The Journal of Cell Biology, (2018) 217:3031-3044.

Src- and confinement-dependent FAK-activation causes E-cadherin relaxation and beta-catenin activity.
C. Gayrard, C. Bernaudin, T. Déjardin, C. Seiler, N. Borghi.
The Journal of Cell Biology, (2018) 217:1063-1077.

Coordination between Intra- and Extracellular Forces Regulates Focal Adhesion Dynamics.
B.R. Sarangi, M. Gupta, B.L. Doss, N. Tissot, F. Lam, R.M. Mège, N. Borghi, B. Ladoux. 
Nano Letters, (2017) 17:399-406.

Experimental approaches in mechanotransduction: From molecules to pathology.
N. Borghi, E. Farge, C. Lavelle.
Methods, (2016) 94:1-3.

FRET-based Molecular Tension Microscopy.
C. Gayrard, N. Borghi.
Methods, (2016) 94:33-42.

FROM THE COVER: Vinculin head-tail interaction defines multiple early mechanisms for stem cell rigidity sensing.
Z. Liu, P. Bun, N. Audugé, M. Coppey-Moisan, N. Borghi.
Integrative Biology, (2016) 8:693-703.

Mechanical checkpoint for persistent cell polarization in adhesion-naive fibroblasts.
P. Bun, J. Liu, H. Turlier, Z. Liu, K. Uriot, J.F. Joanny, M. Coppey-Moisan.
Biophys J, (2014) 107:324-35.
Comment in: Biophys J. (2014) 107:285-6.

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