Our team belongs to "Matieres et Systèmes Complexes" Lab, (CNRS/Paris Diderot University). We are interested in the physics of isolated living cells. In particular, we try to bring out the role of mechanical phenomena within biological processes. For this purpose, we designed a microplates setup enabling us to apply controled forces on isolated cells, but also to measure forces generated by cell themselves (see "Microplates device" section). More particularly, our interest focuses on cell adhesion, geometry and force generation, mechanotransduction of animal and plant cells, and cellular interactions within the immune system.
Over the past few years, many experiments showed that cells are sensitive to mechanical cues. In particular, micro-environmental stiffness can influence complex processes such as migration, proliferation or differentiation. We try to understand the origin of this mecano-sensitivity. Our microplates device enables the measurement of the traction forces generated by single cells durign spreading. We have also designed a unique methode allowing us to dynamically control the rigidity felt by a living cell. We could thus show that the traction force generated by a single cell was adapted to the effective rigidity of the substrate in less than 0.1s. In contrast to well-known biochemical regulation loops, this fast cell-scale response suggests that early cell response to stiffness could be mechanical in nature. Indeed, we could show that the mechanical power (energy per unit time) invested by the cell to bend its substrate was adapted to stiffness, and reflected the force-dependent kinetics of myosin binding to actin (contractile units similar to those involved in muscles). From the physicist point of view, early cell response to stiffness is similar to an impedance matching phenomena where the output of a generator (here the acto-myosin units) is modulated by the load it is facing (here the rigidity of the cell substrate).
Though having the exact same genome, the cells of an organism present very different shapes. These shapes result from complex interactions between internal components (actin cytoskeleton, adhesion complexes, membrane, etc.) and external factors (confinment, matrix rigidity, soluble factors, etc.). We try to understand how a cell interacts with its mechanical environment to get its shape. To do so, we study early spreading of adherent cells, a process during which the cells go from a spherical shape to an isotropic spread shape. In order to correlate physical quantitative measurements to the setting of cell architecture components, we combine traction force measurement between two microplates to evanescent waves fluorescence (TIRF) and confocal imaging. This device also allows us to interrogate cellular mechano-sensitivity, as well as the link existing between traction force and the growth of adhesion complexes in varying mechanical environments.
In the immune system, T lymphocytes, which are key modulators of the immune response, have recently been shown to respond to mechanical changes. T lymphocyte activation requires cell-cell interaction with different cell populations of the immune system, such as dendritic cells, monocytes, macrophages. Yet, little is known about the rigidity of these different antigen presenting cells. This project aims at using the single-cell microplates assay to measure the mechanical properties of human monocyte derived antigen presenting cells. If these cells happen to have different mechanical properties, it may affect T cell activation : cell rigidity could be an important factor in immune cell-cell interactions and T cell mediated responses.