Selective Activation of Cells by Piezoelectric Molybdenum Disulfide Nanosheets with Focused Ultrasound

An accurate method for neural stimulation within the brain could be very useful for treating brain circuit dysfunctions and neurological disorders. With the aim of developing such a method, this study investigated the use of piezoelectric molybdenum disulfide nanosheets (MoS₂NS) to remotely convert ultrasound energy into localized electrical stimulation in vitro and in vivo. The application of ultrasound to cells surrounding MoS₂NS required only a single pulse of 2 MHz ultrasound (400 kPa, 1,000,000 cycles, and 500 ms pulse duration) to elicit significant responses in 37.9 ± 7.4% of cells in terms of fluxes of calcium ions without detectable cellular damage. The proportion of responsive cells was mainly influenced by the acoustic pressure, number of ultrasound cycles, and concentration of MoS₂NS. Tests using appropriate blockers revealed that voltage-gated membrane channels were activated. In vivo data suggested that, with ultrasound stimulation, neurons closest to the MoS₂NS were 3-fold more likely to present c-Fos expression than cells far from the NS. The successful activation of neurons surrounding MoS₂NS suggests that this represents a method with high spatial precision for selectively modulating one or several targeted brain circuits.