High-Resolution Imaging of Intracellular Calcium Fluctuations Caused by Oscillating Microbubbles
Ultrasound insonification of microbubbles can locally enhance drug delivery, but the microbubble–cell interaction remains poorly understood. Because intracellular calcium (Cai2+) is a key cellular regulator, unraveling the Cai2+ fluctuations caused by an oscillating microbubble provides crucial insi...
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| Veröffentlicht in: | Ultrasound in medicine & biology 2020-08, Vol.46 (8), p.2017-2029 |
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| container_title | Ultrasound in medicine & biology |
| container_volume | 46 |
| creator | Beekers, Inés Mastik, Frits Beurskens, Robert Tang, Phoei Ying Vegter, Merel van der Steen, Antonius F.W. de Jong, Nico Verweij, Martin D. Kooiman, Klazina |
| description | Ultrasound insonification of microbubbles can locally enhance drug delivery, but the microbubble–cell interaction remains poorly understood. Because intracellular calcium (Cai2+) is a key cellular regulator, unraveling the Cai2+ fluctuations caused by an oscillating microbubble provides crucial insight into the underlying bio-effects. Therefore, we developed an optical imaging system at nanometer and nanosecond resolution that can resolve Cai2+ fluctuations and microbubble oscillations. Using this system, we clearly distinguished three Cai2+ uptake profiles upon sonoporation of endothelial cells, which strongly correlated with the microbubble oscillation amplitude, severity of sonoporation and opening of cell–cell contacts. We found a narrow operating range for viable drug delivery without lethal cell damage. Moreover, adjacent cells were affected by a calcium wave propagating at 15 μm/s. With the unique optical system, we unraveled the microbubble oscillation behavior required for drug delivery and Cai2+ fluctuations, providing new insight into the microbubble–cell interaction to aid clinical translation. |
| doi_str_mv | 10.1016/j.ultrasmedbio.2020.03.029 |
| format | Article |
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Because intracellular calcium (Cai2+) is a key cellular regulator, unraveling the Cai2+ fluctuations caused by an oscillating microbubble provides crucial insight into the underlying bio-effects. Therefore, we developed an optical imaging system at nanometer and nanosecond resolution that can resolve Cai2+ fluctuations and microbubble oscillations. Using this system, we clearly distinguished three Cai2+ uptake profiles upon sonoporation of endothelial cells, which strongly correlated with the microbubble oscillation amplitude, severity of sonoporation and opening of cell–cell contacts. We found a narrow operating range for viable drug delivery without lethal cell damage. Moreover, adjacent cells were affected by a calcium wave propagating at 15 μm/s. With the unique optical system, we unraveled the microbubble oscillation behavior required for drug delivery and Cai2+ fluctuations, providing new insight into the microbubble–cell interaction to aid clinical translation.</description><identifier>ISSN: 0301-5629</identifier><identifier>EISSN: 1879-291X</identifier><identifier>DOI: 10.1016/j.ultrasmedbio.2020.03.029</identifier><identifier>PMID: 32402676</identifier><language>eng</language><publisher>England: Elsevier Inc</publisher><subject>Cell–cell contact opening ; Confocal microscopy ; Drug delivery ; High-speed imaging ; Intracellular calcium ; Microbubbles ; Sonoporation ; Ultrasound</subject><ispartof>Ultrasound in medicine & biology, 2020-08, Vol.46 (8), p.2017-2029</ispartof><rights>2020 The Authors</rights><rights>Copyright © 2020 The Authors. Published by Elsevier Inc. 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With the unique optical system, we unraveled the microbubble oscillation behavior required for drug delivery and Cai2+ fluctuations, providing new insight into the microbubble–cell interaction to aid clinical translation.</description><subject>Cell–cell contact opening</subject><subject>Confocal microscopy</subject><subject>Drug delivery</subject><subject>High-speed imaging</subject><subject>Intracellular calcium</subject><subject>Microbubbles</subject><subject>Sonoporation</subject><subject>Ultrasound</subject><issn>0301-5629</issn><issn>1879-291X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNqNkEFv1DAQha0KRJeWv1BFnLgkjO1snHCrtpSuVFQJUYmbGTuTxSsnae24Uv89Xm1BHDmNNPPevJmPsfccKg68-bivkl8CxpF64-ZKgIAKZAWiO2Er3qquFB3_8YqtQAIv143oTtnbGPcAoBqp3rBTKWoQjWpW7OeN2_0qv1GcfVrcPBXbEXdu2hXzUGynnGLJ--QxFBv01qWxuPbJLgkP4pibKVJfmOfiLlrnfW5n71dnw2ySMZ7iOXs9oI_07qWesfvrz983N-Xt3Zft5vK2tLUUS2mFaakXdV2LddtLbG2LnWnUoEh2CNLWZOqmEWjVGlGtFWLPieOAddsCkjxjH457H8L8mCguenTxcDxONKeo88cSpOp4l6WfjtJ8ZYyBBv0Q3IjhWXPQB8J6r_8lrA-ENUidCWfzxUtOMnn81_oHaRZcHQWUv31yFHQmQ5Ol3gWyi-5n9z85vwF8GpX2</recordid><startdate>202008</startdate><enddate>202008</enddate><creator>Beekers, Inés</creator><creator>Mastik, Frits</creator><creator>Beurskens, Robert</creator><creator>Tang, Phoei Ying</creator><creator>Vegter, Merel</creator><creator>van der Steen, Antonius F.W.</creator><creator>de Jong, Nico</creator><creator>Verweij, Martin D.</creator><creator>Kooiman, Klazina</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-0905-5422</orcidid></search><sort><creationdate>202008</creationdate><title>High-Resolution Imaging of Intracellular Calcium Fluctuations Caused by Oscillating Microbubbles</title><author>Beekers, Inés ; Mastik, Frits ; Beurskens, Robert ; Tang, Phoei Ying ; Vegter, Merel ; van der Steen, Antonius F.W. ; de Jong, Nico ; Verweij, Martin D. ; Kooiman, Klazina</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c432t-c2b8ed2444258d3a8c8a9b67f7e39a03c4eb4662ac75aa757aad1e1afa4880ae3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Cell–cell contact opening</topic><topic>Confocal microscopy</topic><topic>Drug delivery</topic><topic>High-speed imaging</topic><topic>Intracellular calcium</topic><topic>Microbubbles</topic><topic>Sonoporation</topic><topic>Ultrasound</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Beekers, Inés</creatorcontrib><creatorcontrib>Mastik, Frits</creatorcontrib><creatorcontrib>Beurskens, Robert</creatorcontrib><creatorcontrib>Tang, Phoei Ying</creatorcontrib><creatorcontrib>Vegter, Merel</creatorcontrib><creatorcontrib>van der Steen, Antonius F.W.</creatorcontrib><creatorcontrib>de Jong, Nico</creatorcontrib><creatorcontrib>Verweij, Martin D.</creatorcontrib><creatorcontrib>Kooiman, Klazina</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Ultrasound in medicine & biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Beekers, Inés</au><au>Mastik, Frits</au><au>Beurskens, Robert</au><au>Tang, Phoei Ying</au><au>Vegter, Merel</au><au>van der Steen, Antonius F.W.</au><au>de Jong, Nico</au><au>Verweij, Martin D.</au><au>Kooiman, Klazina</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>High-Resolution Imaging of Intracellular Calcium Fluctuations Caused by Oscillating Microbubbles</atitle><jtitle>Ultrasound in medicine & biology</jtitle><addtitle>Ultrasound Med Biol</addtitle><date>2020-08</date><risdate>2020</risdate><volume>46</volume><issue>8</issue><spage>2017</spage><epage>2029</epage><pages>2017-2029</pages><issn>0301-5629</issn><eissn>1879-291X</eissn><abstract>Ultrasound insonification of microbubbles can locally enhance drug delivery, but the microbubble–cell interaction remains poorly understood. 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| source | Elsevier ScienceDirect Journals |
| subjects | Cell–cell contact opening Confocal microscopy Drug delivery High-speed imaging Intracellular calcium Microbubbles Sonoporation Ultrasound |
| title | High-Resolution Imaging of Intracellular Calcium Fluctuations Caused by Oscillating Microbubbles |
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