Research

Adhesion complexes

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

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

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

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.