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.
Shapiro
Mikhail G
MG
Department of Biological Engineering, Massachusetts Institute of Technology, 150 Albany Street, NW14-2213, Cambridge, Massachusetts 02139, USA.
Szablowski
Jerzy O
JO
Langer
Robert
R
Jasanoff
Alan
A
D015374:Biosensing Techniques / Q000379:methods; D050882:CREB-Binding Protein / Q000737:chemistry / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000737:chemistry / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000032:analysis* / Q000378:metabolism; D005293:Ferritins / Q000737:chemistry* / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods*; D053758:Nanoparticles / Q000737:chemistry*; D010766:Phosphorylation; D017434:Protein Structure, Tertiary
D017362:Cyclic AMP Response Element-Binding Protein; D005293:Ferritins; D050882:CREB-Binding Protein; D017868:Cyclic AMP-Dependent Protein Kinases