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

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)

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.

Different Roles of Cadherins in the Assembly and Structural Integrity of the Desmosome Complex.
M. Lowndes, S. Rakshit, O. Shafraz, N. Borghi, R.M. Harmon, K. Green, S. Sivasankar, and W. J. Nelson.
J. Cell Science, (2014) 127:2339-50.

E-cadherin is under constitutive actomyosin-generated tension that is increased at cell-cell contacts upon externally applied stretch.
N. Borghi, M, Sorokina, O. G. Shcherbakova, W. I. Weis, B. L. Pruitt, W. J. Nelson, A. R. Dunn.
Proc. Natl. Acad. Sci. USA, (2012) 109:12568-73.

FROM THE COVER: Regulation of cell motile behavior by crosstalk between cadherin- and integrin-mediated adhesions
N. Borghi, M. Lowndes, V. Maruthamuthu, M. Gardel and W. J. Nelson.
Proc. Natl. Acad. Sci. USA, (2010) 107:13324-9.
Comment in: Proc. Natl. Acad. Sci. USA, (2010) 107:13199-200.

Intercellular Adhesion in Morphogenesis: Molecular and Biophysical Considerations.
N. Borghi and W.J. Nelson
In “Epithelial Morphogenesis and Tissue Remodelling”, Current Topics in Developmental Biology, (2009) 89:1-32, T. Lecuit (Ed.).

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