Print Email Facebook Twitter High-Resolution Imaging of Intracellular Calcium Fluctuations Caused by Oscillating Microbubbles Title High-Resolution Imaging of Intracellular Calcium Fluctuations Caused by Oscillating Microbubbles Author Beekers, D.I. (Erasmus MC) Mastik, Frits (Erasmus MC) Beurskens, Robert (Erasmus MC) Tang, Phoei Ying (Erasmus MC) Vegter, Merel (Erasmus MC) van der Steen, A.F.W. (TU Delft ImPhys/Medical Imaging; Erasmus MC) de Jong, N. (TU Delft ImPhys/Medical Imaging; Erasmus MC) Verweij, M.D. (TU Delft ImPhys/Medical Imaging; Erasmus MC) Kooiman, Klazina (Erasmus MC) Date 2020 Abstract Ultrasound insonification of microbubbles can locally enhance drug delivery, but the microbubble–cell interaction remains poorly understood. Because intracellular calcium (Cai 2+) is a key cellular regulator, unraveling the Cai 2+ 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 Cai 2+ fluctuations and microbubble oscillations. Using this system, we clearly distinguished three Cai 2+ 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 Cai 2+ fluctuations, providing new insight into the microbubble–cell interaction to aid clinical translation. Subject Cell–cell contact openingConfocal microscopyDrug deliveryHigh-speed imagingIntracellular calciumMicrobubblesSonoporationUltrasound To reference this document use: http://resolver.tudelft.nl/uuid:1c5db92d-95c4-40e0-ba73-ab140f72c6cd DOI https://doi.org/10.1016/j.ultrasmedbio.2020.03.029 ISSN 0301-5629 Source Ultrasound in Medicine & Biology, 46 (8), 2017-2029 Part of collection Institutional Repository Document type journal article Rights © 2020 D.I. Beekers, Frits Mastik, Robert Beurskens, Phoei Ying Tang, Merel Vegter, A.F.W. van der Steen, N. de Jong, M.D. Verweij, Klazina Kooiman Files PDF 1_s2.0_S0301562920301459_main.pdf 2.86 MB Close viewer /islandora/object/uuid:1c5db92d-95c4-40e0-ba73-ab140f72c6cd/datastream/OBJ/view