Biophysical Society Thematic Meeting | Bucharest 2026

Biophysics of Membrane Reactions in Brian

Wednesday Speaker Abstracts

LIGHT-CONTROLLED MODULATION OF NEURONAL EXCITABILITY USING PHOTOSWITCHABLE LIPIDS Simon Strassgschwandtner; Rohit Yadv; Juergen Pfeffermann; Peter Pohl ; Johannes Kepler University, Linz, Austria The mechanosensitive two-pore-domain potassium channel TRAAK functions as a K ⁺ leak channel in neurons, where it contributes to setting the resting membrane potential and thereby regulates action potential generation and neuronal excitability. Light-driven perturbations of the lipid bilayer may therefore provide a means to control excitability by (i) modulating mechanosensitive leak conductances or (ii) transiently displacing membrane charge. Here, photoswitchable lipids are used to realize both complementary strategies for optical control of neuronal excitability. In the first approach, photolipid photoisomerization alters membrane capacitance on millisecond timescales, generating optocapacitive currents. In cellular membranes, these currents induce transient depolarization or hyperpolarization, depending on the wavelength of the incident light. UV-induced increases in membrane capacitance are sufficient to activate voltage-gated sodium channels and trigger action potentials, whereas blue light decreases capacitance and, via photolipid-induced membrane tension, may activate mechanosensitive channels (Bassetto et al. 2024. Photolipid excitation triggers depolarizing optocapacitive currents and action potentials. Nat. Commun. 15(1):1139). The latter mechanism is examined in the second approach using the mechanosensitive channel TRAAK as a model system. Reconstitution of TRAAK into lipid bilayers establishes a well-defined membrane environment devoid of cytoskeletal constraints. Incorporation of the azobenzene-based photolipid OptoDArG enables reversible, light-driven modulation of membrane tension. TRAAK activation following photolipid cis–trans isomerization is characterized at the single-molecule level in planar lipid bilayers and at the ensemble level in membrane blisters and whole-GUV patch-clamp recordings. These measurements elucidate the role of background membrane tension in TRAAK gating. Together, these results establish photoswitchable lipids as versatile tools for optically modulating neuronal excitability by targeting membrane reactions that couple mechanics, electrostatics, and ion channel function.

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