Original Contribution| Volume 49, ISSUE 5, P1153-1163, May 2023

Intercellular Calcium Waves and Permeability Change Induced by Vertically Deployed Surface Acoustic Waves in a Human Cerebral Microvascular Endothelial Cell Line (hCMEC/D3) Monolayer

  • Ming-Yen Hsiao
    Corresponding author. Department of Physical Medicine and Rehabilitation, College of Medicine, National Taiwan University, No. 7, Zhongshan South Road, Zhongzheng District, Taipei City 100, Taiwan.
    Department of Physical Medicine and Rehabilitation, College of Medicine, National Taiwan University, Taipei, Taiwan

    Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital, Taipei, Taiwan
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  • Defei Liao
    Thomas Lord Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC, USA
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  • Gaoming Xiang
    Thomas Lord Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC, USA
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  • Pei Zhong
    Thomas Lord Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC, USA
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      The ultrasound-mediated blood–brain barrier (BBB) opening with microbubbles has been widely employed, while recent studies also indicate the possibility that ultrasound alone can open the BBB through a direct mechanical effect. However, the exact mechanisms through which ultrasound interacts with the BBB and whether it can directly trigger intracellular signaling and a permeability change in the BBB endothelium remain unclear.


      Vertically deployed surface acoustic waves (VD-SAWs) were applied on a human cerebral microvascular endothelial cell line (hCMEC/D3) monolayer using a 33-MHz interdigital transducer that exerts shear stress-predominant stimulation. The intracellular calcium response was measured by fluorescence imaging, and the permeability of the hCMEC/D3 monolayer was assessed by transendothelial electrical resistance (TEER).


      At a certain intensity threshold, VD-SAWs induced an intracellular calcium surge that propagated to adjacent cells as intercellular calcium waves. VD-SAWs induced a TEER decrease in a pulse repetition frequency-dependent manner, thereby suggesting possible involvement of the mechanosensitive ion channels.


      The unique VD-SAW system enables more physiological mechanical stimulation of the endothelium monolayer. Moreover, it can be easily combined with other measurement devices, providing a useful platform for further mechanistic studies on ultrasound-mediated BBB opening.


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