A Membrane-Targeted Push-Pull Azobenzene for the Optical Modulation of the Membrane Potential

In the last years, the use of light as a tool for modulating membrane potential and bioelectricity has emerged as a fascinating opportunity, with the broad aim of establishing life-machine symbiosis that can help in healing disorders and restoring biological functions. An approach to induce light sensitivity in animal cells, which are usually transparent to visible light, is the use of photoactuators. These are photoactive materials that can decorate or localize into the cell membrane and are able to transduce light into a signal that can be processed by the cells. A variety of materials are suitable for the non-genetic optostimulation of cells, ranging from inorganic nanoparticles to organic polymer films and nanostructures.<br/>The cell membrane and its electrical potential represent the core of bioelectricity, hence constituting an ideal target for exogenous modulation of signalling. For this reason, we chose a push-pull azobenzene molecule (PP-2Pyr) as a membrane-targeting photoactuator that induces a charge displacement upon isomerization. The work comprises the photophysical characterization of the photoactuator, focusing on the isomerization dynamics, and the evaluation of the photoinduced effects on HEK-293 cells. The focus is on unveiling the photostimulation mechanism, intending to link the photophysical changes occurring in the molecular photoactuator after light absorption, to the biological effects on <i>in vitro</i> cell models. The proposed light-driven mechanism originates from inferences on the molecular partitioning of PP-2Pyr in the two membrane leaflets and on the rearrangement of the charges adsorbed to the membrane due to variations in the molecular dipole moment upon light excitation.