Membrane-targeted molecule for cell optostimulation.
Magni A., Paternó G. M., Moschetta M., Zucchi A., Mattiello S., Mattioli G., Beverina L., Lanzani G.
Light-driven modulation of cellular activity with high spatial and temporal resolution is becoming of great interest. We are considering the use of light-sensitive molecules that act as photo-actuators avoiding genetic manipulation. We present the characterization of a newly synthesized conjugated molecule (BV-1) which spontaneously partitions into lipid bilayers owing to its amphiphilicity. We performed steady-state and time-resolved spectroscopic measurements revealing the presence of a charge-transfer state upon visible light irradiation and the possibility for BV-1 to undergo intersystem-crossing towards a triplet state, which can transfer energy to molecular oxygen. $In vitro$ experiments shows that BV-1 has low toxicity in dark conditions, while the illumination with visible light induces membrane poration and permeabilization, which leads to a robust depolarization in HEK cells and a phototoxic effect in $E.coli$ cultures. Our data suggest the occurrence of two independent light-driven mechanisms for the increase of the membrane permeabilization: i) lipid peroxidation within the cell membrane and ii) conformational reorganization of BV-1 altering the integrity of the membrane.