Ultrasound Mediated Cellular Deflection Results in Cellular Depolarization

Abstract

Ultrasound has been used to manipulate cells in both humans and animal models. While intramembrane cavitation and lipid clustering have been suggested as likely mechanisms, they lack experimental evidence. Here, high‐speed digital holographic microscopy (kiloHertz order) is used to visualize the cellular membrane dynamics. It is shown that neuronal and fibroblast membranes deflect about 150 nm upon ultrasound stimulation. Next, a biomechanical model that predicts changes in membrane voltage after ultrasound exposure is developed. Finally, the model predictions are validated using whole‐cell patch clamp electrophysiology on primary neurons. Collectively, it is shown that ultrasound stimulation directly defects the neuronal membrane leading to a change in membrane voltage and subsequent depolarization. The model is consistent with existing data and provides a mechanism for both ultrasound‐evoked neurostimulation and sonogenetic control.

Sonogenetic control of mammalian cells using exogenous Transient Receptor Potential A1 channels

“…However, these responses are significantly smaller than those observed in hsTRPA1-expressing neurons, and ultrasoundevoked action potentials were rarely detected at the frequency and pressures tested. Additionally, the infrequent responses in control neurons in vitro could be a result of membrane deflection as we recently showed 64 , or a result of interactions with the substrate, or with the patch pipette in electrophysiology 65 . Control neurons have been previously shown to generate action potentials upon ultrasound stimuli at lower fundamental frequencies, however, these responses required repeated pulses 4 .…”

Pressure and ultrasound activate mechanosensitive TRAAK K+channels through increased membrane tension

“…Instead, acoustic radiation force and resulting acoustic streaming likely account for mechanical activation of channels by ultrasound 25,35,38 . Indeed, work in other systems has demonstrated analogous mechanical displacements of reconstituted lipid bilayers and cell membranes 38,39 .…”

Ultrasound Neuromodulation as a New Brain Therapy

“…Recent data indicate direct mechanically induced depolarization effects. [ 10 ] Ultrasound can produce very small cell membrane deflections (150 nm) which change membrane voltage and lead to subsequent depolarizations. Other work on disconnected single neurons implies that ultrasound effects are stronger with higher peak pressures and effects are also evident with ultrashort pressure pulses (4 µs) as applied by TPS.…”