Sensitization of Transforming Growth Factor-β Signaling by Multiple Peptides Patterned on DNA Nanostructures

We report sensitization of a cellular signaling pathway by addition of functionalized DNA nanostructures. Signaling by transforming growth factor beta (TGF beta) has been shown to be dependent on receptor clustering. By patterning a DNA nanostructure with closely spaced peptides that bind to TGF beta receptor, we observe increased sensitivity of NMuMG cells to TGF beta ligand. This is evidenced by translocation of secondary messenger proteins to the nucleus and stimulation of an inducible luciferase reporter at lower concentrations of TGF beta ligand. We believe this represents an important initial step toward realization of DNA as a self-assembling and biologically compatible material for use in tissue engineering and drug delivery.