Physical approaches to cell dynamics and tissue morphogenesis
Group leader : P.F. Lenne
Our group aims at determining how mechanical and physical interactions are organized at cell surfaces in vivo and how these interactions are processed to produce cell and tissue responses.
The making of an organism relies on interactions at cell surfaces and communication between cells. How are mechanical and physical interactions organized at cell surfaces in vivo ? How are these interactions processed to produce cell and tissue responses? We tackle these questions by combining physical and genetic/molecular approaches. In particular we study how cell behaviours such as cell shape changes and cell polarity emerge from the mesoscopic (between the microscopic and macroscopic scales) properties of cell surface and interfaces in vivo.
Our work is multidisciplinary and integrates physical/mechanical and molecular/genetic approaches. In particular we develop microscopes to observe subcellular structures at high resolution, measure molecular interactions and probe the local mechanics of cells. We also use modelling to make quantitative and falsifiable predictions, which we test experimentally. Modelling is also a guide for new experiments. We hope that such approaches may shed light on fundamental mechanisms of Life and will be useful for medical applications (imaging and tissue engineering).
Our group aims at determining how mechanical and physical interactions are organized at cell surfaces in vivo and how these interactions are processed to produce cell and tissue responses. To tackle these broad questions, we focus on two aspects of tissue morphogenesis, namely cell polarization and force transmission in fields of cells. More specifically we study:
(1) the assembly and dynamics of adhesion complexes at cell interfaces in vivo ;
(2) the mechanics of cell interfaces and force transmission in a tissue ;
(3) the molecular interactions during tissue polarization in vivo.
We are using Drosophila and C. Elegans as models systems to address questions (1-2) and question (3), respectively. The originality of our project relies in the integration of both physics (optics/microscopy/mechanics/modelling) and experimental biology to study quantitatively tissue morphogenesis.
1. Assembly and dynamics of adhesion complexes at cell interfaces in vivo
Cell-cell adhesion requires the formation of finite clusters where adhesion is concentrated. Moreover, subcellular tensile forces are coupled to and transmitted at adhesive clusters. These clusters are mechanically regulated. Thus, understanding the organization/dynamics of such clusters is an essential step. We study quantitatively the supramolecular organisation of cadherins (E- and N-cadherin) in the early embryonic epithelium and in the pupal retina of Drosophila by combining super-resolution imaging, dynamic Imaging and modeling.
2. Mechanics of cell interfaces and force transmission in a tissue
During the formation of tissues, cells divide, change their shape and their position, or die.
This small set of mechanisms determines the shape and the size of tissues. While we know a great deal about the genes which orchestrate these mechanisms, we do not know much about the physical forces which ‘sculpt’ the tissues. What are the forces that cells generate to shape the tissues? In collaboration with the group of Thomas Lecuit, we have recently shown that force generators act at cell surfaces to produce local remodeling of cell contacts (Rauzi et al, 2008, 2010).
Yet, how coupling through adhesive clusters change and regulate the mechanics of tissues and therefore force propagation is poorly understood. Using micromanipulation (e.g. optical tweezers) and force sensors, we try to tackle this question.
3. Quantitative map of molecular interactions during tissue polarization in vivo
How do animal tissues acquire specific polarity axes during morphogenesis? While gradients of signaling molecules have been suggested to play a role in this process, our understanding of the mechanisms underlying tissue polarization is still very partial. In particular we lack quantitative data on the behaviour and interactions between the molecular players, such as ligands and their receptors, during the polarization process in vivo. We recently teamed up with the group of Vincent Bertrand (IBDM) to tackle this question in C. Elegans.
By combining quantitative Imaging and genetic perturbation, we aim at mapping the distribution/dynamics of Wnt ligands, of receptors and of their interactions during the polarisation of a tissue in vivo
March 3rd, 2015
Direct laser manipulation reveals the mechanics of cell contacts in vivo.
October 29th, 2013
Principles of E-Cadherin Supramolecular Organization In Vivo.
August 17th, 2012
Bond flexibility and low valence promote finite clusters of self-aggregating particles.
December 1st, 2008
Nature and anisotropy of cortical forces orienting Drosophila tissue morphogenesis.
July 22nd, 2015
Calcium Spikes in Epithelium: study on Drosophila early embryos.
January 8th, 2015
Superresolution measurements in vivo: imaging Drosophila embryo by photoactivated localization microscopy.
August 22nd, 2014
Probing cell mechanics with subcellular laser dissection of actomyosin networks in the early developing Drosophila embryo.
August 1st, 2014
Clustering of low-valence particles: structure and kinetics.
May 5th, 2014
Setting-up a simple light sheet microscope for in toto imaging of C. elegans development.
February 18th, 2014
Membrane microdomains: from seeing to understanding.
February 22nd, 2013
Cortical forces in cell shape changes and tissue morphogenesis.
May 1st, 2012
Calcium signaling in developing embryos: focus on the regulation of cell shape changes and collective movements.
March 2nd, 2011
FCS diffusion laws in two-phase lipid membranes: determination of domain mean size by experiments and Monte Carlo simulations.
January 1st, 2011
Force generation, transmission, and integration during cell and tissue morphogenesis.
December 23rd, 2010
Planar polarized actomyosin contractile flows control epithelial junction remodelling.
September 1st, 2009
Probing cell-surface dynamics and mechanics at different scales.
November 1st, 2008
Fluorescence fluctuations analysis in nanoapertures: physical concepts and biological applications.
September 1st, 2008
Raft nanodomains contribute to Akt/PKB plasma membrane recruitment and activation.
June 5th, 2008
A two-tiered mechanism for stabilization and immobilization of E-cadherin.
August 1st, 2007
Cell surface mechanics and the control of cell shape, tissue patterns and morphogenesis.
July 26th, 2006
Dynamic molecular confinement in the plasma membrane by microdomains and the cytoskeleton meshwork.
September 9th, 2005