Fig. 6: Proposed mechanism of light-driven cellular depolarization.

a Sketch of the membrane lipid bilayer showing the preferential localization of the MTP2 molecules in the inner leaflet, as the molecular dipole moment tends to align to the electric field. b Snapshots of the system simulated with a voltage of −200 mV, starting (top) and final (bottom) conformation; orange and green MTP2 molecules represent the molecules bounded to the outer and inner leaflet at t = 0, respectively; water and lipid acyl chains are not reported for clarity. c Number of molecules moving from the outer to the inner leaflet during CG-MD simulations at different transmembrane voltages. d Plot showing the amplitude of the light-induced membrane depolarization as a function of the resting membrane potential in HEK293T cells, loaded with 10 μM MTP2 and stimulated with 20 ms 470 nm-light pulses at 105 mWmm⁻². The dashed line represents the linear regression curve of the plotted data points (R² = 0.88). e Sketch illustrating the MTP2 mechanism of light-driven membrane potential modulation in cells. The molecule is internalized within the membrane (left). When light is shined on the cells, an additional dipole moment appears (centre), which induces a redistribution of charges and an inward current across the membrane (right)