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Title: Mechanically induced integrin ligation mediates intracellular calcium signaling with single pulsating cavitation bubbles
Authors: Li, Fenfang
Park, Tae Hyun
Sankin, George
Gilchrist, Christopher
Liao, Defei
Chan, Chon U.
Mao, Zheng
Hoffman, Brenton D.
Zhong, Pei
Keywords: Science::Medicine
Issue Date: 2021
Source: Li, F., Park, T. H., Sankin, G., Gilchrist, C., Liao, D., Chan, C. U., Mao, Z., Hoffman, B. D. & Zhong, P. (2021). Mechanically induced integrin ligation mediates intracellular calcium signaling with single pulsating cavitation bubbles. Theranostics, 11(12), 6090-6104.
Journal: Theranostics
Abstract: Therapeutic ultrasound or shockwave has shown its great potential to stimulate neural and muscle tissue, where cavitation microbubble induced Ca2+ signaling is believed to play an important role. However, the pertinent mechanisms are unknown, especially at the single-cell level. Particularly, it is still a major challenge to get a comprehensive understanding of the effect of potential mechanosensitive molecular players on the cellular responses, including mechanosensitive ion channels, purinergic signaling and integrin ligation by extracellular matrix. Methods: Here, laser-induced cavitation microbubble was used to stimulate individual HEK293T cells either genetically knocked out or expressing Piezo1 ion channels with different normalized bubble-cell distance. Ca2+ signaling and potential membrane poration were evaluated with a real-time fluorescence imaging system. Integrin-binding microbeads were attached to the apical surface of the cells at mild cavitation conditions, where the effect of Piezo1, P2X receptors and integrin ligation on single cell intracellular Ca2+ signaling was assessed. Results: Ca2+ responses were rare at normalized cell-bubble distances that avoided membrane poration, even with overexpression of Piezo1, but could be increased in frequency to 42% of cells by attaching integrin-binding beads. We identified key molecular players in the bead-enhanced Ca2+ response: increased integrin ligation by substrate ECM triggered ATP release and activation of P2X-but not Piezo1-ion channels. The resultant Ca2+ influx caused dynamic changes in cell spread area. Conclusion: This approach to safely eliciting a Ca2+ response with cavitation microbubbles and the uncovered mechanism by which increased integrin-ligation mediates ATP release and Ca2+ signaling will inform new strategies to stimulate tissues with ultrasound and shockwaves.
ISSN: 1838-7640
DOI: 10.7150/thno.56813
Rights: © 2021 The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License ( See for full terms and conditions.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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