Sensitization of nerve cells to ultrasound stimulation through Piezo1-targeted microbubbles

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, docume...

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Main Authors: Xuelian Shen, Zhuqing Song, Erjiao Xu, Jun Zhou, Fei Yan
Format: Article
Language:English
Published: Elsevier 2021-05-01
Series:Ultrasonics Sonochemistry
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1350417721000353
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author Xuelian Shen
Zhuqing Song
Erjiao Xu
Jun Zhou
Fei Yan
author_facet Xuelian Shen
Zhuqing Song
Erjiao Xu
Jun Zhou
Fei Yan
author_sort Xuelian Shen
collection DOAJ
description 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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spelling doaj.art-e574cc14b1904a60845b426815b75f372022-12-21T17:15:12ZengElsevierUltrasonics Sonochemistry1350-41772021-05-0173105494Sensitization of nerve cells to ultrasound stimulation through Piezo1-targeted microbubblesXuelian Shen0Zhuqing Song1Erjiao Xu2Jun Zhou3Fei Yan4Department 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, ChinaDepartment of Breast Surgery, Peking University Shenzhen Hospital, Shenzhen 518036, ChinaDepartment of Medical Ultrasonics, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518033, ChinaDepartment of Ultrasound, The First College of Clinical Medical Science, China Three Gorges University, Yi Chang, Hubei 443000, China; Corresponding authors.CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China; Corresponding authors.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.http://www.sciencedirect.com/science/article/pii/S1350417721000353NeuromodulationUltrasound stimulationMicrobubblesPiezo1Ca2+ transients
spellingShingle Xuelian Shen
Zhuqing Song
Erjiao Xu
Jun Zhou
Fei Yan
Sensitization of nerve cells to ultrasound stimulation through Piezo1-targeted microbubbles
Ultrasonics Sonochemistry
Neuromodulation
Ultrasound stimulation
Microbubbles
Piezo1
Ca2+ transients
title Sensitization of nerve cells to ultrasound stimulation through Piezo1-targeted microbubbles
title_full Sensitization of nerve cells to ultrasound stimulation through Piezo1-targeted microbubbles
title_fullStr Sensitization of nerve cells to ultrasound stimulation through Piezo1-targeted microbubbles
title_full_unstemmed Sensitization of nerve cells to ultrasound stimulation through Piezo1-targeted microbubbles
title_short Sensitization of nerve cells to ultrasound stimulation through Piezo1-targeted microbubbles
title_sort sensitization of nerve cells to ultrasound stimulation through piezo1 targeted microbubbles
topic Neuromodulation
Ultrasound stimulation
Microbubbles
Piezo1
Ca2+ transients
url http://www.sciencedirect.com/science/article/pii/S1350417721000353
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