Research

Adhesion complexes

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Reconstituted adhesion machinery

We study the molecular bases of mechanosensing and mechanotransduction at cadherin-mediated adherens junctions. To answer these questions, we have developed acellular systems coupling recombinant adhesion protein micropatterning and actin polymerization in vitro, allowing us to reconstitute in a controlled manner minimal cell adhesion structures and associated molecular mechanosensors. Coupling these protein biochemistry-based model systems with advanced microscopy, and force application/detection devices will allow us to determine the biochemical, biophysical and mechanical parameters of adhesions-associated molecular mechanosensors.

Single Cells

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Force sensing in cells

We study force sensing and mechanotransduction at integrin-mediated cell-extracellular matrix and cadherin-mediated cell-cell adhesions. To answer these questions, we have developed single cells and cell doublets models allowing a tight control of cell-matrix and cell-adhesion formation in a physically and mechanically defined microenvironment. Coupled with advanced microscopy, microforce sensor devices and classical cell biology, these approaches will allow us to determine the molecular mechanisms that control cell adhesions remodeling and their adaptation to environment compliance as well as to cytoskeleton visco-elastic properties and cell’s internal tension generated by myosin motors.

Cell assemblies

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Dynamics of epithelial sheets

We study the collective behavior of cells in the context of tissue homeostasis but also in cell polarity and migration. To answer these questions, we are developing micro- and nanofabricated tools and micromanipulation to control the mechanical environment of cells. These tools are combined with molecular approaches and advanced techniques in light microscopy to study the influence of physical properties of the environment on collective cell migration and the organization of epithelial layers. We are characterizing how physical constraints can lead to emergent dynamical and mechanical properties of various epithelial tissues. Along this line, we develop mechanobiological models to better understand the cellular responses to their mechanical environment.

Tissues

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Intestinal epithelium homeostasis

We study how differentiating epithelial cells (renal, intestinal, epidermal or cancerous), integrating microenvironment cues (extracellular matrix chemistry, rigidity, geometry and topography), maintain cohesion, and establish and maintain apico-basal polarity. Our aims are to determine i) how physical constraints of the microenvironment modulate mechanical properties of epithelial cells and tissues, ii) how they direct a variety of cell behaviors including stem cell proliferation, cell migration, differentiation, and polarity, and iii) how they impact on the morphogenesis normal epithelial tissue, as well as the pathological development of intestinal rare diseases. Biomimetic substrates coupled to high resolution imaging and biochemistry are instrumental to reach these goals.

Partners

Collaborations

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International

Alexandre Kabla
Cambridge University, UK

Xavier Trepat
IBEC, Spain

Alpha Yap
University of Queensland, Australia

Julia Yeomans
Oxford University, UK

Michael Sheetz
Pakorn tony Kanchanawong
Lim chwee Teck
Yusuke Tonama
Yan Jie
Gianluca Grenci
Mechanobiology Institute (MBI), Singapore

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National

France

Raphael Voituriez, Philippe Marcq
Sorbonne Université, Paris

Sylvie Hénon
Laboratoire Matière et Systèmes Complexes, Université de Paris

Philippe Chavrier, Christophe Lamaze, Jacques Prost
Institut Curie, Paris 

Olivier Goulet
Hôpital Necker-Enfants Malades, Paris

Yong Chen
Ecole Normale Supérieure, Département de Chimie, Paris

Bénédicte Dalaval
CRBM, Montpellier

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Title

Internal

Nicolas Borghi
Mechanotransduction: from Cell Surface to Nucleus

Nicolas Minc
Cellular Spatial Organization

Guillaume Romet-Lemonne & Antoine Jégou
Regulation of Actin Assembly Dynamics

René-marc Mège & Benoît Ladoux

INSTITUT JACQUES MONOD
Université Paris Diderot / CNRS

15 rue Hélène Brion - Building Buffon
75205 Paris Cedex 13 - France

René-Marc Mège

Benoît Ladoux

+33 (0)157278071