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Ultrasonic Control of Neural Activity through Activation of the Mechanosensitive Channel MscL

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    Ultrasonic Control of Neural Activity through Activation of the Mechanosensitive Channel MscL
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    • Jia Ye
      Jia Ye
      Children’s Hospital and Department of Biophysics, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China
      More by Jia Ye
    • Siyang Tang
      Siyang Tang
      Children’s Hospital and Department of Biophysics, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China
      More by Siyang Tang
    • Long Meng
      Long Meng
      Paul C. Lauterbur Research Center for Biomedical Imaging, Shenzhen Key Laboratory for MRI, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518005, China
      More by Long Meng
    • Xia Li
      Xia Li
      Children’s Hospital and Department of Biophysics, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China
      More by Xia Li
    • Xiaoxu Wen
      Xiaoxu Wen
      Children’s Hospital and Department of Biophysics, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China
      More by Xiaoxu Wen
    • Sihan Chen
      Sihan Chen
      Children’s Hospital and Department of Biophysics, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China
      More by Sihan Chen
    • Lili Niu
      Lili Niu
      Paul C. Lauterbur Research Center for Biomedical Imaging, Shenzhen Key Laboratory for MRI, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518005, China
      More by Lili Niu
    • Xiangyao Li
      Xiangyao Li
      Children’s Hospital and Department of Biophysics, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China
      More by Xiangyao Li
    • Weibao Qiu
      Weibao Qiu
      Paul C. Lauterbur Research Center for Biomedical Imaging, Shenzhen Key Laboratory for MRI, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518005, China
      More by Weibao Qiu
    • Hailan Hu
      Hailan Hu
      Children’s Hospital and Department of Biophysics, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China
      More by Hailan Hu
    • Mizu Jiang
      Mizu Jiang
      Children’s Hospital and Department of Biophysics, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China
      More by Mizu Jiang
    • Shiqiang Shang
      Shiqiang Shang
      Children’s Hospital and Department of Biophysics, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China
      More by Shiqiang Shang
    • Qiang shu
      Qiang shu
      Children’s Hospital and Department of Biophysics, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China
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    • Hairong Zheng*
      Hairong Zheng
      Paul C. Lauterbur Research Center for Biomedical Imaging, Shenzhen Key Laboratory for MRI, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518005, China
      *E-mail: [email protected]
      More by Hairong Zheng
    • Shumin Duan
      Shumin Duan
      Children’s Hospital and Department of Biophysics, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China
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    • Yuezhou Li*
      Yuezhou Li
      Children’s Hospital and Department of Biophysics, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China
      *E-mail: [email protected]
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      Orcidhttp://orcid.org/0000-0003-0582-4255
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    Nano Letters

    Cite this: Nano Lett. 2018, 18, 7, 4148–4155
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    https://doi.org/10.1021/acs.nanolett.8b00935
    Published June 19, 2018
    Copyright © 2018 American Chemical Society
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    Abstract

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    Externally controlling the excitation of a neuronal subset through ion channels activation can modulate the firing pattern of an entire neural circuit in vivo. As nanovalves in the cell membrane, ion channels can be opened by light (optogenetics) or ultrasonic (sonogenetics) means. A thoroughly analyzed force sensor is the Escherichia colimechanosensitive channel of large conductance (MscL). Here we expressed MscL in rat hippocampal neurons in a primary culture and showed that it could be activated by low-pressure ultrasound pulses. The gain-of-function mutation, I92L, sensitized MscL’s sonic response, triggering action potentials at a peak negative pressure as low as 0.25 MPa. Further, the I92L MscL reliably elicited individual spikes by timed brief pulses, making excitation programmable. Because MscL opens to tension in the lipid bilayer, requiring no other proteins or ligands, it could be developed into a general noninvasive sonogenetic tool to manipulate the activities of neurons or other cells and potential nanodevices.

    Copyright © 2018 American Chemical Society

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    • Expression of MscL has minimal effects on membrane properties; none of ultrasound-induced activations were detected in early days of cultured hippocampal cells; no effect of ultrasound on background mCherry fluorescence; calcein flux though gated I92L channels; ultrasound-induced activation was independent of the amount of buffer used in the surface-acoustic-wave-based ultrasound device (PDF)

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    Cite this: Nano Lett. 2018, 18, 7, 4148–4155
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    https://doi.org/10.1021/acs.nanolett.8b00935
    Published June 19, 2018
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