Protein Nanoparticles Engineered to Sense Kinase Activity in MRI
We introduce a family of protein nanoparticles capable of sensing analytes in conjunction with magnetic resonance imaging (MRI). The new sensors are derived from the iron storage protein ferritin (Ft); they are designed and optimized using facile protein engineering methods, and self-assembled in cells harboring specific combinations of DNA coding sequences. As illustration, we show that suitably constructed Ft-based sensors can report activity of the important neural signaling enzyme protein kinase A (PKA). Phosphorylation of the engineered Ft-based nanoparticles by PKA promotes clustering and changes in T_2-weighted MRI signal.
© 2009 American Chemical Society. Received November 12, 2008. Publication Date (Web): January 29, 2009. The authors thank Michael Greenberg for supplying clones for CREB and CBP, and thank Paolo Arioso for providing the human HF and LF genes. The authors are also grateful to Niyatee Samudra for assistance with DNA cloning and Vibhu Sachdev for help obtaining TEM images. M.G.S. wishes to acknowledge the Fannie and John Hertz Foundation and the Paul and Daisy Soros Fellowship for generous support. This work was funded in part by a New Innovator Award NIH DP2-OD2441 to A.J., and NIH grant number R01-DE013023- 08 to R.L.
Supplemental Material - ja8086938_si_001.pdf
Accepted Version - nihms91943.pdf