Ultrasound Mediated Cellular Deflection Results in Cellular Depolarization

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.

Automated summary

The study utilized high-speed digital holographic microscopy to visualize cellular membrane dynamics under ultrasound stimulation and found that both neuronal and fibroblast membranes deflect about 150 nm. A biomechanical model predicting changes in membrane voltage after ultrasound exposure was developed and validated using whole-cell patch clamp electrophysiology. The results demonstrate that ultrasound stimulation directly induces defects in neuronal membranes, leading to changes in membrane voltage.