Shen X(1), Song Z(2), Xu E(3), Zhou J(4), Yan F(5). Author information:
(1)Department of Medical Ultrasonics, The Eighth Affiliated Hospital, Sun
Yat-sen University, Shenzhen, 518033, China; Department of Ultrasound, The First
College of Clinical Medical Science, China Three Gorges University, Yi Chang,
Hubei 443000, China.
(2)Department of Breast Surgery, Peking University Shenzhen Hospital, Shenzhen
(3)Department of Medical Ultrasonics, The Eighth Affiliated Hospital, Sun
Yat-sen University, Shenzhen, 518033, China.
(4)Department of Ultrasound, The First College of Clinical Medical Science,
China Three Gorges University, Yi Chang, Hubei 443000, China. Electronic
(5)CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of
Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy
of Sciences, Shenzhen, 518055, China. Electronic address: [Email]
Neuromodulation by ultrasound (US) has recently drawn considerable attention due to its great advantages in noninvasiveness, high penetrability across the skull and highly focusable acoustic energy. However, the mechanisms and safety from US irradiation still remain less understood. Recently, documents revealed Piezo1, a mechanosensitive cation channel, plays key role in converting mechanical stimuli from US through its trimeric propeller-like structure. Here, we developed a Piezo1-targeted microbubble (PTMB) which can bind to the extracellular domains of Piezo1 channel. Due to the higher responsiveness of bubbles to mechanical stimuli from US, significantly lower US energy for these PTMB-binding cells may be needed to open these mechanosensitive channels. Our results showed US energy at 0.03 MPa of peak negative pressure can achieve an equivalent level of cytoplasmic Ca2+ transients which generally needs 0.17 MPa US intensity for the control cells. Cytoplasmic Ca2+ elevations were greatly reduced by chelating extracellular calcium ions or using the cationic ion channel inhibitors, confirming that US-mediated calcium influx are dependent on the Piezo1 channels. No bubble destruction and obvious temperature increase were observed during the US exposure, indicating cavitation and heating effects hardly participate in the process of Ca2+ transients. In conclusion, our study provides a novel strategy to sensitize the response of nerve cells to US stimulation, which makes it safer application for US-mediated neuromodulation in the future.
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