Group leaders : Christophe Le Clainche
and Louis Renault
Our aim is to understand the molecular and physical mechanisms producing force and cell movement, by directed polymerization of cytoskeletal polymers – actin filaments and microtubules – in response to cell signalling. These motile processes are essential for cell migration and tumor invasion, embryo development, immune response, synapse plasticity, tissue repair, and the spread of intracellular pathogens. Our strategy is to analyze, biochemically, the control of these polymers’ dissipative self-assembly by regulatory proteins, in combination with a biomimetic/biophysical “bottom-up” approach: we reconstitute self-organizing, autonomous motile systems, mimicking cell reality. To address these issues at the interface between biology, physics, and chemistry, we are an interdisciplinary group, composed of molecular biologists, biochemists, structuralists, and biophysicists.
A multidisciplinary approach to understand the elementary mechanisms regulating actin assembly
Research directions : Control of filament vectorial assembly by proteins interacting with actin ; Control of nucleation and processive assembly by protein machineries coupled to signalling pathways (proteins WASP-Arp2/3, formins, Spire/Eg6, IQGAP1) ; Propulsive movement of functionalized microbeads and giant liposomes initiating actin polymerization ;Measure of individual filament dynamics ; Measure of membrane deformation induced by its interaction with active polymers ; Reconstitution of filament assembly in cell-matrix adhesions ; Molecular mechanism coordinating the turnover of different actin networks during cell migration.
Methods and expertise : Protein expression (in bacteria and baculovirus), purification from tissue ; thermodynamics and fast kinetics (stopped-flow) of protein-protein interaction mechanisms and self-assembly ; crystallography and structural analysis ; spectrofluorometry and light scattering ; optical video microscopy (phase contrast, fluorescence, evanescent wave, optical traps, laser tracking) and image analysis ; functionalization of particles and lipid vesicles ; force measurements.