TY - JOUR
T1 - Sensing intracellular calcium ions using a manganese-based MRI contrast agent
AU - Barandov, Ali
AU - Bartelle, Benjamin B.
AU - Williamson, Catherine G.
AU - Loucks, Emily S.
AU - Lippard, Stephen J.
AU - Jasanoff, Alan
N1 - Funding Information:
Project funding was provided by NIH grants R01-DA038642, R21-MH102470, BRAIN Initiative awards U01-NS090451, U01-NS103470, and UF1-NS107712, and an MIT Simons Center for the Social Brain Seed Grant to A.J., as well as R01-GM065519 to S.J.L. We acknowledge the Department of Chemistry Instrumentation Facility for use of analytical equipment and also thank Miyeko D. Mana for assistance with the 3D gel experiments and Souparno Ghosh for additional support with tissue culture experiments.
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Calcium ions are essential to signal transduction in virtually all cells, where they coordinate processes ranging from embryogenesis to neural function. Although optical probes for intracellular calcium imaging have been available for decades, the development of probes for noninvasive detection of intracellular calcium signaling in deep tissue and intact organisms remains a challenge. To address this problem, we synthesized a manganese-based paramagnetic contrast agent, ManICS1-AM, designed to permeate cells, undergo esterase cleavage, and allow intracellular calcium levels to be monitored by magnetic resonance imaging (MRI). Cells loaded with ManICS1-AM show changes in MRI contrast when stimulated with pharmacological agents or optogenetic tools; responses directly parallel the signals obtained using fluorescent calcium indicators. Introduction of ManICS1-AM into rodent brains furthermore permits MRI-based measurement of neural activation in optically inaccessible brain regions. These results thus validate ManICS1-AM as a calcium sensor compatible with the extensive penetration depth and field of view afforded by MRI.
AB - Calcium ions are essential to signal transduction in virtually all cells, where they coordinate processes ranging from embryogenesis to neural function. Although optical probes for intracellular calcium imaging have been available for decades, the development of probes for noninvasive detection of intracellular calcium signaling in deep tissue and intact organisms remains a challenge. To address this problem, we synthesized a manganese-based paramagnetic contrast agent, ManICS1-AM, designed to permeate cells, undergo esterase cleavage, and allow intracellular calcium levels to be monitored by magnetic resonance imaging (MRI). Cells loaded with ManICS1-AM show changes in MRI contrast when stimulated with pharmacological agents or optogenetic tools; responses directly parallel the signals obtained using fluorescent calcium indicators. Introduction of ManICS1-AM into rodent brains furthermore permits MRI-based measurement of neural activation in optically inaccessible brain regions. These results thus validate ManICS1-AM as a calcium sensor compatible with the extensive penetration depth and field of view afforded by MRI.
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U2 - 10.1038/s41467-019-08558-7
DO - 10.1038/s41467-019-08558-7
M3 - Article
C2 - 30796208
AN - SCOPUS:85061958805
SN - 2041-1723
VL - 10
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 897
ER -