Photolipid excitation triggers depolarizing optocapacitive currents and action potentials

Carlos A. Z. Bassetto, Juergen Pfeffermann, Rohit Yadav, Simon Strassgschwandtner, Toma Glasnov, Francisco Bezanilla () and Peter Pohl ()
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Carlos A. Z. Bassetto: The University of Chicago
Juergen Pfeffermann: Johannes Kepler University Linz
Rohit Yadav: Johannes Kepler University Linz
Simon Strassgschwandtner: Johannes Kepler University Linz
Toma Glasnov: Karl-Franzens-University
Francisco Bezanilla: The University of Chicago
Peter Pohl: Johannes Kepler University Linz

Nature Communications, 2024, vol. 15, issue 1, 1-13

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-45403-y

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