Membrane-Targeted Molecules for Cell Optostimulation

Light-driven modulation of cellular activity with both high spatial and temporal resolution is becoming an increasingly active research area. Existing approaches, such as optogenetics, have shown promising results and, as an alternative, we envision the use of light-sensitive molecules that act as photo-actuators avoiding genetic manipulation.<br/>We are interested in investigating the effects of different photo-actuators, such as azobenzene-based photochromic and donor-acceptor molecules. These compounds are designed to satisfy the following requirements: (i) absorb light in the visible or near-infrared window of the spectrum; (ii) spontaneously and efficiently partition into the lipid bilayers owing to their amphiphilicity, (iii) exhibit low toxicity in dark condition and preferentially also under illumination.<br/>We combine the observation of the photoinduced effects on both HEK-293 cells and primary neurons, which are evaluated by exploiting electrophysiology, while steady-state and time-resolved optical spectroscopies reveal their photophysics and functioning mechanism.<br/>Taken together, our data allows us to identify different light-driven mechanisms, responsible for the photoinduced effects observed on cells. These include, for instance, (i) the thinning or thickening of the membrane due to conformational changes in the molecules, (ii) the increase of the membrane permeabilization, and the formation of pore-like structures likely due to the lipid peroxidation following the photosensitization of singlet oxygen within the cell membrane, (iii) the rearrangement of the charges adsorbed to the membrane due to variations in the molecular dipole moment.