Optogenetic control of cell behaviour (MechanoSwitch)

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Cellular decision-making in complex environments depends on both biochemical and mechanical signals. It is now well established that adherent cells generate mechanical forces to sense the adhesive geometry and rigidity of their environment, with dramatic consequences for migration, differentiation and fate. Usually the cellular response to stiffness is studied in a static context, for example by measuring cellular traction forces and mechanotransduction on elastic substrates of variable stiffness. It is however less clear how rigidity sensing works when cells and their environment interact in a dynamical context, although this is the standard case in development, wound healing or metastasis. The MechanoSwitch project will use recent advances in optogenetics to unravel how living cells use their sense of touch in a dynamical way and how cell behaviour can be controled by light. We will use optical microscopy to live-image cell organization, soft elastic substrates and traction force microscopy to continuously monitor cell forces, and optogenetics to dynamically change the contractile status of the cell. Mathematical models for cell organization and migration will be first parametrized by the experimental data and then used to design the new round of experiments. By predicting the appropriate illumination patterns for optogenetics, we plan to steer cells in complex environments.