Deciphering Ephrin/Eph signaling pathways in cancer cells using rationally designed ligand nanoclusters

The dynamic link between the nanoscale spatial distribution of biomolecules and their functional impact on cellular and downstream biological behaviors has been hypothesized, but only supported by limited evidences. This is mostly due to the lack to methods to fabricate well-defined patterns of biomolecules. In this thesis, we utilized the DNA origami method to create protein ligand and antigen patterns with high precision, and applied it to study cell signaling events in a cancer cell line and complex antibody-antigen interactions. In addition, to achieve quality fabrication of our protein and antigen functionalized DNA origami nanostructures we developed and adapted several DNA and protein purification methods. Finally, we employed the versatility of the DNA origami method to create anticancer drug carriers with tunable drug release kinetics.

List of scientific papers

I. Shaw, A.; Lundin, V.; Petrova, E.; Fördős, F.; Benson, E.; Al-Amin, A.; Herland, A.; Blokzijl, A.; Högberg, B.; Teixeira, A. I. Spatial Control of Membrane Receptor Function Using Ligand Nanocalipers. Nat Methods. 2014, 11, 841–846.
https://doi.org/10.1038/nmeth.3025

II. Shaw, A.; Högberg, B. Resolving Peculiar Antibody-Antigen Interactions with Patterned Surface Plasmon Resonance. [Manuscript]

III. Shaw, A.; Benson, E.; Högberg, B. Purification of Functionalized DNA Origami Nanostructures. ACS Nano. 2015, 9, 4968–4975.
https://doi.org/10.1021/nn507035g

IV. Zhao, Y.-X.; Shaw, A.; Zeng, X.; Benson, E.; Nyström, A. M.; Högberg, B. DNA Origami Delivery System for Cancer Therapy with Tunable Release Properties. ACS Nano. 2012, 6, 8684–8691.
https://doi.org/10.1021/nn3022662