Reversible Ca2+ signaling and enhanced paracellular transport in endothelial monolayer induced by acoustic bubbles and targeted microbeads
Ultrasound and microbubble mediated blood brain barrier opening is a non-invasive and effective technique for drug delivery to targeted brain region. However, the exact mechanisms are not fully resolved. The influences of Ca2+ signaling on sonoporation and endothelial tight junctional regulation aff...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-01-01
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| Series: | Ultrasonics Sonochemistry |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1350417724004309 |
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| author | Jiawei Lin Chaofeng Qiao Hao Jiang Zhihui Liu Yaxin Hu Wei Liu Yu Yong Fenfang Li |
| author_facet | Jiawei Lin Chaofeng Qiao Hao Jiang Zhihui Liu Yaxin Hu Wei Liu Yu Yong Fenfang Li |
| author_sort | Jiawei Lin |
| collection | DOAJ |
| description | Ultrasound and microbubble mediated blood brain barrier opening is a non-invasive and effective technique for drug delivery to targeted brain region. However, the exact mechanisms are not fully resolved. The influences of Ca2+ signaling on sonoporation and endothelial tight junctional regulation affect the efficiency and biosafety of the technique. Therefore, an improved understanding of how ultrasound evokes Ca2+ signaling in the brain endothelial monolayer, and its correlation to endothelial permeability change is necessary. Here, we examined the effects of SonoVue microbubbles or integrin-targeted microbeads on ultrasound induced bioeffects in brain microvascular endothelial monolayer using an acoustically-coupled microscopy system, where focused ultrasound exposure and real-time recording of Ca2+ signaling and membrane perforation were performed. Microbubbles induced robust Ca2+ responses, often accompanied by cell poration, while ultrasound with microbeads elicited reversible Ca2+ response without membrane poration. At the conditions evoking reversible Ca2+ signaling, intracellular Ca2+ release and reactive oxygen species played key roles for microbubbles induced Ca2+ signaling while activation of mechanosensitive ion channels was essential for the case of microbeads. Trans-well diffusion analysis revealed significantly higher trans-endothelial transport of 70 kDa FITC-dextran for both integrin-targeted microbeads and microbubbles compared to the control group. Further immunofluorescence staining showed disruption of cell junctions with microbubble stimulation and reversible remodeling of many cell junctions by ultrasound with integrin-targeted microbeads. This investigation provides new insights for ultrasound induced Ca2+ signaling and its influence on endothelial permeability, which may help develop new strategies for safe and efficient drug/gene delivery in the vascular system. |
| format | Article |
| id | doaj-art-9d74dd7bc7c045a7a1e177381aca5d2f |
| institution | Kabale University |
| issn | 1350-4177 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ultrasonics Sonochemistry |
| spelling | doaj-art-9d74dd7bc7c045a7a1e177381aca5d2f2025-01-11T06:38:45ZengElsevierUltrasonics Sonochemistry1350-41772025-01-01112107181Reversible Ca2+ signaling and enhanced paracellular transport in endothelial monolayer induced by acoustic bubbles and targeted microbeadsJiawei Lin0Chaofeng Qiao1Hao Jiang2Zhihui Liu3Yaxin Hu4Wei Liu5Yu Yong6Fenfang Li7Institute of Biomedical Engineering, Shenzhen Bay Laboratory, Shenzhen, ChinaInstitute of Biomedical Engineering, Shenzhen Bay Laboratory, Shenzhen, ChinaInstitute of Biomedical Engineering, Shenzhen Bay Laboratory, Shenzhen, ChinaInstitute of Biomedical Engineering, Shenzhen Bay Laboratory, Shenzhen, ChinaSchool of Biomedical Engineering, Shenzhen University, Shenzhen, ChinaSchool of Electronics and Information Engineering, Harbin Institute of Technology, Shenzhen, ChinaInstitute of Biomedical Engineering, Shenzhen Bay Laboratory, Shenzhen, ChinaInstitute of Biomedical Engineering, Shenzhen Bay Laboratory, Shenzhen, China; Corresponding author.Ultrasound and microbubble mediated blood brain barrier opening is a non-invasive and effective technique for drug delivery to targeted brain region. However, the exact mechanisms are not fully resolved. The influences of Ca2+ signaling on sonoporation and endothelial tight junctional regulation affect the efficiency and biosafety of the technique. Therefore, an improved understanding of how ultrasound evokes Ca2+ signaling in the brain endothelial monolayer, and its correlation to endothelial permeability change is necessary. Here, we examined the effects of SonoVue microbubbles or integrin-targeted microbeads on ultrasound induced bioeffects in brain microvascular endothelial monolayer using an acoustically-coupled microscopy system, where focused ultrasound exposure and real-time recording of Ca2+ signaling and membrane perforation were performed. Microbubbles induced robust Ca2+ responses, often accompanied by cell poration, while ultrasound with microbeads elicited reversible Ca2+ response without membrane poration. At the conditions evoking reversible Ca2+ signaling, intracellular Ca2+ release and reactive oxygen species played key roles for microbubbles induced Ca2+ signaling while activation of mechanosensitive ion channels was essential for the case of microbeads. Trans-well diffusion analysis revealed significantly higher trans-endothelial transport of 70 kDa FITC-dextran for both integrin-targeted microbeads and microbubbles compared to the control group. Further immunofluorescence staining showed disruption of cell junctions with microbubble stimulation and reversible remodeling of many cell junctions by ultrasound with integrin-targeted microbeads. This investigation provides new insights for ultrasound induced Ca2+ signaling and its influence on endothelial permeability, which may help develop new strategies for safe and efficient drug/gene delivery in the vascular system.http://www.sciencedirect.com/science/article/pii/S1350417724004309UltrasoundCavitation microbubblesIntegrin-targeted microbeadsBlood–brain barrierCa2+ signalingCell junctions remodeling |
| spellingShingle | Jiawei Lin Chaofeng Qiao Hao Jiang Zhihui Liu Yaxin Hu Wei Liu Yu Yong Fenfang Li Reversible Ca2+ signaling and enhanced paracellular transport in endothelial monolayer induced by acoustic bubbles and targeted microbeads Ultrasonics Sonochemistry Ultrasound Cavitation microbubbles Integrin-targeted microbeads Blood–brain barrier Ca2+ signaling Cell junctions remodeling |
| title | Reversible Ca2+ signaling and enhanced paracellular transport in endothelial monolayer induced by acoustic bubbles and targeted microbeads |
| title_full | Reversible Ca2+ signaling and enhanced paracellular transport in endothelial monolayer induced by acoustic bubbles and targeted microbeads |
| title_fullStr | Reversible Ca2+ signaling and enhanced paracellular transport in endothelial monolayer induced by acoustic bubbles and targeted microbeads |
| title_full_unstemmed | Reversible Ca2+ signaling and enhanced paracellular transport in endothelial monolayer induced by acoustic bubbles and targeted microbeads |
| title_short | Reversible Ca2+ signaling and enhanced paracellular transport in endothelial monolayer induced by acoustic bubbles and targeted microbeads |
| title_sort | reversible ca2 signaling and enhanced paracellular transport in endothelial monolayer induced by acoustic bubbles and targeted microbeads |
| topic | Ultrasound Cavitation microbubbles Integrin-targeted microbeads Blood–brain barrier Ca2+ signaling Cell junctions remodeling |
| url | http://www.sciencedirect.com/science/article/pii/S1350417724004309 |
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