Photolipid excitation triggers depolarizing optocapacitive currents and action potentials

Abstract

Optically-induced changes in membrane capacitance may regulate neuronal activity without requiring genetic modifications. Previously, they mainly relied on sudden temperature jumps due to light absorption by membrane-associated nanomaterials or water. Yet, nanomaterial targeting or the required high infrared light intensities obstruct broad applicability. Now, we propose a very versatile approach: photolipids (azobenzene-containing diacylglycerols) mediate light-triggered cellular de- or hyperpolarization. As planar bilayer experiments show, the respective currents emerge from millisecond-timescale changes in bilayer capacitance. UV light changes photolipid conformation, which awards embedding plasma membranes with increased capacitance and evokes depolarizing currents. They open voltage-gated sodium channels in cells, generating action potentials. Blue light reduces the area per photolipid, decreasing membrane capacitance and eliciting hyperpolarization. If present, mechanosensitive channels respond to the increased mechanical membrane tension, generating large depolarizing currents that elicit action potentials. Membrane self-insertion of administered photolipids and focused illumination allows cell excitation with high spatiotemporal control. HighlightsO_LIRapid photolipid photoisomerization generates optocapacitive currents in planar lipid bilayers and HEK293 cells. C_LIO_LIThese currents originate from photo-induced changes in membrane capacitance C_LIO_LIUV light-triggered membrane depolarization opens NaV1.3, evoking action potentials. C_LIO_LIBlue light-induced mechanosensitive channel opening gives rise to depolarizing currents, which may evoke NaV1.3-mediated action potentials. C_LI