Medically Advanced Devices Laboratory, Department of Mechanical and Aerospace Engineering, Jacobs School of Engineering and Department of Surgery, School of Medicine, University of California San Diego, La Jolla, CA, 92093, USA.
Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, 92037, USA.
Adv Sci (Weinh). 2022 Jan;9(2):e2101950. doi: 10.1002/advs.202101950. Epub 2021 Nov 7.
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.
超声已被用于在人类和动物模型中操纵细胞。虽然有人提出跨膜空化和脂质聚集可能是其作用机制，但缺乏实验证据。在这里，高速数字全息显微镜（千赫兹级）被用于可视化细胞膜动力学。结果表明，神经元和成纤维细胞膜在超声刺激下会发生约 150nm 的偏转。接下来，开发了一种生物力学模型，用于预测超声暴露后细胞膜电压的变化。最后，使用原代神经元的全细胞膜片钳电生理学验证了模型预测。总的来说，研究结果表明，超声刺激直接使神经元细胞膜发生变形，导致细胞膜电压的变化和随后的去极化。该模型与现有数据一致，为超声激发神经刺激和超声基因控制提供了一种机制。
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