Research

 

 

 

 

At the single cells level

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 allow us to determine the molecular mechanisms that control cell adhesion and cytoskeleton remodeling, as well as cell shape and migration and their adaptation to environment compliance as well as to cytoskeleton visco-elastic properties and cell’s internal tension generated by myosin motors.

 

At the cell assemblies level

 

We study the collective behavior of cells in epithelial sheets, in the context of tissue homeostasis and wound healing. To answer these questions, we developing microfabricated tools   and biophysical tools to measure and control the mechanical properties and topology of cell’s microenvironment. These tools are combined with molecular approaches, advanced techniques in light microscopy, image analysis and modeling to study the influence of physical properties of the environment on the organization of epithelial layers, collective cell migration, single and collective cell polarization, cell division and cell extrusion. We are characterizing how physical constraints can lead to emergent dynamical and mechanical properties of various epithelial tissues.

 

 

At the tissues and organoid level

 

We study how more complex epithelial tissues formed of mixed populations of cells (normal/adhesion deficient, normal/cancer, differentiation/stem cells) facing homogeneous and heterogeneous substrates (extracellular matrix chemistry, rigidity, geometry and topography), regulate homeostasis, segregate and/or auto assemble. 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 extrusion or delamination, 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.

 

 

Collaborations:

 

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

National:

France

Raphael VoituriezPhilippe Marcq
Sorbonne Université, Paris

Sylvie Hénon
Laboratoire Matière et Systèmes Complexes, Université de Paris

Philippe ChavrierChristophe LamazeJacques Prost
Institut Curie, Paris 

Olivier Goulet
Hôpital Necker-Enfants Malades, Paris

Yong Chen
Ecole Normale Supérieure, Département de Chimie, Paris

Bénédicte Dalaval
CRBM, Montpellier

 

Internal

Nicolas Borghi
Mechanotransduction: from Cell Surface to Nucleus

Nicolas Minc
Cellular Spatial Organization

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

 

 

Fundings: