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bioRxiv · 10.1101/2023.11.20.567805

An enclosed live-imaging platform to reveal ultrasound-inflicted mechanolysis and wound healing response

Bai, Z.·Li, Z.·Shao, Y.
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Abstract

Focused ultrasound (FUS) has been widely adopted in medical and life science researches. Although various physical and biological effects of FUS have been well-documented, there is still a lack of understanding and direct evidence on the biological mechanism of therapeutic cell ablation caused by high-intensity ultrasound (HIFU) and the subsequent wound healing responses. This study develops an enclosed cell culture device that synergistically combines non-invasive FUS stimulation and real-time, on-the-fly live-cell imaging, providing an in vitro platform to explore short and long-term biological effects of ultrasound. The process, mechanism, and wound healing response of cell ablation induced by HIFU are elucidated, revealing a unique mechanism, termed ultrasound-inflicted cellular mechanolysis, that is mediated by growing subcellular cavitation air bubbles under confined contact with cells. This provides a previously unappreciated mechanism for understanding the biomechanical principles of ultrasound-based ablative therapy. We also reveal a post-ablation phantom layer that serves as a guiding cue for collective cell migration during wound healing, thereby providing a biomimetic model for studying wound healing after HIFU-inflicted damage. Together, this study provides theoretical and technological basis for advancing our understanding of the biological effects of ultrasound-based ablative therapy and inspiring clinically relevant applications in the future. Key Points1) Development of an integrated platform for real-time, on-the-fly imaging of FUS-induced cell ablation and response processes at cellular and subcellular levels 2) Focused ultrasound induces cellular mechanolysis through previously unappreciated subcellular cavitation bubbles that grow under confined contact with cells 3) Post-ablation phantom cell layer could serve as a guiding cue for collective wound healing after ultrasound-inflicted ablation

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Bai, Z., Li, Z., Shao, Y.. 2023-11-20. An enclosed live-imaging platform to reveal ultrasound-inflicted mechanolysis and wound healing response. https://doi.org/10.1101/2023.11.20.567805

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