Our research focuses primarily on the study of populations of interacting cells (from bacteria to epithelial cells) using physics concepts and techniques.
We therefore address fundamental problems of biology from a different perspective, complementary to the biological point of view. More specifically, we are presently involved in two main projects addressing different aspects of communication between cells, thus leading to collective behaviors: chemotaxis of bacteria and collective migration of epithelial cells. In both cases, we make use of the possibilities offered by the techniques of microfabrication: by a good control of the geometries and surface properties, we obtain highly reproducible situations with well defined boundary conditions. The microfabrication techniques we use are mainly based on soft lithography, and develop new strategies allowing such a control. These projects are quite relevant to a number of practical situations in which cells develop a collective response to natural microenvironments (biofilms, tissues, tumors…). The model systems that we develop are a first step towards the understanding of these behaviors.
Chemotaxis of bacteria
E. coli is not only chemotactic, i.e. this bacterium swims towards a source of attractants (food, oxygen…), it also expresses some of these attractants. This property presents some similarities with a classical physics problem: interacting particles submitted to an external field. It gives rise to complex behaviors (pattern formation, self-concentrations, phase transitions…). This out-of-equilibrium system, from the statistical physics point of view, is also at the origin of concentration waves that can be easily observed in suspensions in microchannels. We can tune several parameters (external fields, geometries of the channels…) and observe the propagation of concentration fronts (figure 1) in order to understand the rules governing the behavior of this system.
In the near future, we plan to study more in depth the nature of these concentration waves for instance by inserting obstacles in their way.
video 1 : Propagation of a bacteria concentration wave (E. coli) in a microchannel. velocity of the wave : 4 um/s. width of the channel 500 um. depth : 100 um
Collective migration of epithelial cells
By using an original injury-free technique developed in our group, we can release free surface to a confluent epithelium without damaging the cells (figure 2).
Under these conditions, they spread and migrate on this newly available substrate. The cells keeping cell-cell contacts, this motility has collective properties that give rise to unusual characteristics and in particular, a strong fingering of the newly created border and the apparition of “leader” cells that have very distinct features (figure 3).
The similarity of some of these observations with multicellular clusters stemming out of epithelial tumors in vivo is an incentive to develop a tridimensional equivalent. We have started the first experiments in that direction. In all these situations, various quantities are measured from subcellular to multicellular scales (forces developed by the cells, displacements and velocity fields (figure 4), shapes or polarities…), and are correlated to the relevant biochemical signals, such as oxygen consumption or activity of small G-proteins.
This highly parallel and quantitative approach enables us to efficiently interact with theory groups in order to interpret our experiments and model these out-of-equilibrium phenomena.
Video 2 Migration of an epithelial monolayer on free surface (MDCK cells; video duration 33hr; initial wound width 400 µm)
- See Pascal’s talk at the Curie international course “Multiscale integration on biological systems” (2014): Collective cell migration
- See Pascal’s talk at KITP Santa Barbara (2014): Imposing and releasing a constraint to an epithelium