Super-Resolution Microscopy with a Mechanosensitive Membrane Tension Probe

Abstract

Imaging physical forces in living system remains technically challenging. Newly designed oligothiophenes fluorescent probes exhibiting ground-state planarization at room temperature have led to the development of push-pull probes as mechanosensitive molecules, called “flippers”, suited for FLIM (fluorescence lifetime imaging). These probes insert easily into lipid membranes, where they display red-shifted absorption and a much stronger fluorescence emission in the liquid ordered (Lo) lipid phase than in the liquid disordered (Ld) phase due to the forces imposing a planarization of the chromophore already in its ground state. in this contribution, we evaluate different flipper derivatives for single-molecule based super-resolution imaging and report to our knowledge for the first time imaging below the diffraction limit with mechanosensitive probes using the PAINT method (Point Accumulation for Imaging in Nanoscale Tomography). This work paves the way to the imaging of local forces with nanometric precision in cell biology.