Professor Björn Högberg, Department of Medical Biochemistry and Biophysics, Karolinska Institute

Patterning ligands on the nanoscale with DNA origami - Notch-signaling and Nanorobot therapeutics

My lab uses DNA origami to fold molecularly precise nanostructures. We then use these to scaffold display of nanoscale patterns of protein or peptide ligands that target cell surface receptors. This allows us to investigate how patterns of ligands influence signaling. Is spacing on the nanoscale important; is multivalency important? Using these devices, we have recently discovered that the Notch receptor appears to activate without applying a pulling-force. Instead, we find that multivalency and increased time of residence at the receptor are sufficient for the activation of the Notch pathway. In a similar experiment, we use TRAIL-mimicking peptides that induce clustering of death receptors, this clustering then leads to apoptosis. With this knowledge we have proceeded to fabricate an origami robotic device that displays cytotoxic patterns of these peptides which induces killing of solid tumors in a subcutaneous mouse model.