PhD defense : Cécile Vincent
18
SEP 2025
SEP 2025
Hello everyone,
I will be defending my PhD thesis on September 18 at 3:00 PM in the Charpak Amphitheater. The defense will be held in French.
You are all very welcome!
Title : A biomimetic approach of cell-cell communication
Abstract :
Intercellular communication refers to all the processes by which cells exchange chemical or electrical information. This communication is fundamental to the coordination of cells within developing tissues, determining their form and function. In tissues, GAP junctions, protein nanotunnels perforating cell membranes, play a central role in ensuring ionic and molecular transport between neighboring cells. As some GAP junctions are mechanosensitive, this transport can be altered by mechanical stresses within the tissue. To study the physical principles of intercellular transport across such junctions, and its coupling to mechanical stress, we have developed a biomimetic approach. Tissues are mimicked by two-dimensional networks of aqueous droplets stabilized by phospholipids in oil. Once in contact, these droplets form lipid bilayers called Droplet Interface Bilayers (DIBs) mimicking cell membranes. These bilayers can be functionalized with protein nanopores to reproduce the permeability of GAP junctions.
In this manuscript, we present the experimental methods we have developed to fabricate compact 2D arrays of DIBs, into which a few source drops containing fluorophores are inserted. When alpha-hemolysin nanopores are embedded in the membranes, the fluorophores diffuse into the networks, and we quantified their diffusion by epifluorescence microscopy. We explored the effect of nanopore concentration on transport. This diffusion process is modelled by continuous-time random walks with an exponentially distributed waiting time. This model makes it possible to fit the temporal evolution of concentration profiles and extract a characteristic time that depends non-linearly on nanopore concentration.
Secondly, we introduced mechanosensitive pores (Mscl) into these droplet networks, using synthetic biology protocols for out-of-cell protein expression. In parallel, we developed an experimental set-up for imposing oscillating compressive mechanical strains on the droplet networks, in order to study the coupling between mechanical stress and molecular transport. Our initial results show that the rheological properties of the network are viscoelastic, with a damping length that decreases with excitation frequency. We propose a heuristic rheological model to describe the observed network deformations.
