Achieving Cell Optostimulation with Membrane-Targeted Molecules

In the last years, different non-genetic approaches have been proposed to obtain the light-driven modulation of cellular activity. A variety of different photoactive materials can be exploited as photo transducers, converting the light stimulus into a mechanical, thermal, electrical, or chemical stimulus that can be recognized by cells and tissues.<br/>We are interested in using small organic molecules as photoswitches. Molecules have been designed and synthesized 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/>The observation and the evaluation of the photoinduced effects of the different molecules on both HEK-293 cells, primary neurons, and bacteria strains, together with the photophysical characterization of the aforementioned molecules, lead to the identification of different light-driven mechanisms that allow us to control and manipulate the cell activity.<br/>The photoinduced effects observed on cells are found to be related, for instance, to (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.