Ti₃C₂T_<i>x</i> MXene Flakes for Optical Control of Neuronal Electrical Activity

Understanding cellular electrical communications in both health and disease necessitates precise subcellular electrophysiological modulation. Nanomaterial-assisted photothermal stimulation was demonstrated to modulate cellular activity with high spatiotemporal resolution. Ideal candidates for such an application are expected to have high absorbance at the near-infrared window, high photothermal conversion efficiency, and straightforward scale-up of production to allow future translation. Here, we demonstrate two-dimensional Ti₃C₂T<i>_<i>x</i></i> (MXene) as an outstanding candidate for remote, nongenetic, optical modulation of neuronal electrical activity with high spatiotemporal resolution. Ti₃C₂T<i>_<i>x</i></i>'s photothermal response measured at the single-flake level resulted in local temperature rises of 2.31 ± 0.03 and 3.30 ± 0.02 K for 635 and 808 nm laser pulses (1 ms, 10 mW), respectively. Dorsal root ganglion (DRG) neurons incubated with Ti₃C₂T<i>_<i>x</i></i> film (25 μg/cm²) or Ti₃C₂T<i>_<i>x</i></i> flake dispersion (100 μg/mL) for 6 days did not show a detectable influence on cellular viability, indicating that Ti₃C₂T<i>_<i>x</i></i> is noncytotoxic. DRG neurons were photothermally stimulated using Ti₃C₂T<i>_<i>x</i></i> films and flakes with as low as tens of microjoules per pulse incident energy (635 nm, 2 μJ for film, 18 μJ for flake) with subcellular targeting resolution. Ti₃C₂T<i>_<i>x</i></i>'s straightforward and large-scale synthesis allows translation of the reported photothermal stimulation approach in multiple scales, thus presenting a powerful tool for modulating electrophysiology from single-cell to additive manufacturing of engineered tissues.