We are interested in mechanosensitive fluorescent probes to image forces in living systems. We are particularly interested in membrane tension because it is of much interest to biologist but invisible by fluorescence imaging. Our original design focuses on probes that change color like lobsters during cooking, that is a so new combination of planarization and polarization in the ground state.
The currently best planarizable push-pull or "flipper" probe is a twisted, mechanosensitive dithienothiophene dimer with chalcogen-bonding turn-on D/A switches. Planarization by mechanical forces results in red shifted absorption and increased fluorescence lifetimes. This allows for unprecedented FLIM imaging of membrane tension in GUVs and live cells. This breakthrough invites for diverse applications to (many) open biological questions, to the development of strategies to localize flipper probes in cells (organelles, membrane proteins), and to mechanophores with improved properties and ultimately to probes that operate with new mechanisms (papillons, dynamers).
These projects respond to fundamental needs in the life sciences waiting for solutions from chemistry. The perspective to contribute solutions is very exciting.
Methods: These projects generate much expertise in total synthesis. Probe characterization involves spectroscopic (absorption / fluorescence) and (optional) microscopy (CLSM, FLIM, TPEM) studies in solutions, vesicles (LUVs / GUVs), and cells.
Collaborations: These projects connect to the NCCR Chemical Biology, with close collaboration with other members, NCCR group meetings and retreats. Interdisciplinary (post)doctoral studies in both chemistry and biology groups are possible. They also offer optional in-house collaboration possibilities with regard to computational chemistry and ultrafast photophysics.
Some recent graphical abstracts: