Fluorescent Flippers: Small-Molecule Probes to Image Membrane Tension in Living Systems

Flipper probes have been introduced as small molecule fluorophores to image physical forces, that is, membrane tension in living systems. Their emergence over one decade is described, from evolution in design and synthesis to spectroscopic properties. Responsiveness to physical compression in equilibrium at the ground state is identified as the ideal origin of mechanosensitivity to image membrane tension in living cells. A rich collection of flippers is described to deliver and release in any subcellular membrane of interest in a leaflet-specific manner. Chalcogen-bonding cascade switching and dynamic covalent flippers are developed for super-resolution imaging and dual-sensing of membrane compression and hydration. Availability and broad use in the community validate flipper probes as a fine example of the power of translational supramolecular chemistry, moving from fundamental principles to success on the market.

Automated summary

Flipper probes have been introduced as small molecule fluorophores for imaging physical forces in living systems. The article describes their evolution in design and synthesis as well as their spectroscopic properties. Mechanosensitivity to image membrane tension in living cells is identified as their ideal origin. A variety of flippers have been developed for specific delivery and release in subcellular membranes, enabling super-resolution imaging and dual-sensing of membrane compression and hydration. The availability and broad use of flipper probes validate their power in translational supramolecular chemistry.