Calcium-sensitive MRI contrast agents based on superparamagnetic iron oxide nanoparticles and calmodulin
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- Tatjana Atanasijevic
- Departments of †Nuclear Science and Engineering and
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- Maxim Shusteff
- Biological Engineering Division, and
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- Peter Fam
- Francis Bitter Magnet Laboratory, Massachusetts Institute of Technology, 150 Albany Street, NW14-2213, Cambridge, MA 02139
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- Alan Jasanoff
- Departments of †Nuclear Science and Engineering and
書誌事項
- 公開日
- 2006-10-03
- DOI
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- 10.1073/pnas.0606749103
- 公開者
- National Academy of Sciences
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説明
<jats:p> We describe a family of calcium indicators for magnetic resonance imaging (MRI), formed by combining a powerful iron oxide nanoparticle-based contrast mechanism with the versatile calcium-sensing protein calmodulin and its targets. Calcium-dependent protein–protein interactions drive particle clustering and produce up to 5-fold changes in <jats:italic>T2</jats:italic> relaxivity, an indication of the sensors' potency. A variant based on conjugates of wild-type calmodulin and the peptide M13 reports concentration changes near 1 μM Ca <jats:sup>2+</jats:sup> , suitable for detection of elevated intracellular calcium levels. The midpoint and cooperativity of the response can be tuned by mutating the protein domains that actuate the sensor. Robust MRI signal changes are achieved even at nanomolar particle concentrations (<1 μM in calmodulin) that are unlikely to buffer calcium levels. When combined with technologies for cellular delivery of nanoparticulate agents, these sensors and their derivatives may be useful for functional molecular imaging of biological signaling networks in live, opaque specimens. </jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 103 (40), 14707-14712, 2006-10-03
National Academy of Sciences
