Annals of Biomedical Engineering

, Volume 46, Issue 1, pp 48–59 | Cite as

Low-Intensity Ultrasound Modulates Ca2+ Dynamics in Human Mesenchymal Stem Cells via Connexin 43 Hemichannel

  • Chi Woo Yoon
  • Hayong Jung
  • Kyosuk Goo
  • Sunho Moon
  • Kweon Mo Koo
  • Nan Sook Lee
  • Andrew C. Weitz
  • K. Kirk ShungEmail author


In recent years, ultrasound has gained attention in new biological applications due to its ability to induce specific biological responses at the cellular level. Although the biophysical mechanisms underlying the interaction between ultrasound and cells are not fully understood, many agree on a pivotal role of Ca2+ signaling through mechanotransduction pathways. Because Ca2+ regulates a vast range of downstream cellular processes, a better understanding of how ultrasound influences Ca2+ signaling could lead to new applications for ultrasound. In this study, we investigated the mechanism of ultrasound-induced Ca2+ mobilization in human mesenchymal stem cells using 47 MHz focused ultrasound to stimulate single cells at low intensities (~ 110 mW/cm2). We found that ultrasound exposure triggers opening of connexin 43 hemichannels on the plasma membrane, causing release of ATP into the extracellular space. That ATP then binds to G-protein-coupled P2Y1 purinergic receptors on the membrane, in turn activating phospholipase C, which evokes production of inositol trisphosphate and release of Ca2+ from intracellular stores.


Calcium signaling Mechanotransduction Purinergic signaling ATP 



This work was supported by the National Institutes of Health under Grant No. P41-EB002182 to Dr. K. Kirk Shung. We thank Hae Gyun Lim and Nestor Cabrera Muñoz for their help on the transducer fabrication. We thank Madison Zitting for proofreading.

Supplementary material

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Supplementary material 1 (DOCX 12 kb)
10439_2017_1949_MOESM2_ESM.avi (1.6 mb)
Supplementary material 2 (AVI 1600 kb)
10439_2017_1949_MOESM3_ESM.avi (843 kb)
Supplementary material 3 (AVI 843 kb)


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Copyright information

© Biomedical Engineering Society 2017

Authors and Affiliations

  1. 1.Department of Biomedical EngineeringUniversity of Southern CaliforniaLos AngelesUSA
  2. 2.Institute for Biomedical TherapeuticsUniversity of Southern CaliforniaLos AngelesUSA

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