Docking of Antibodies into Cavities in DNA Origami

Immobilized antibodies are extensively employed for medical diagnostics such as in enzyme-linked immunosorbent assays. Despite their widespread use the ability to control the orientation on surfaces of immobilized antibodies is very limited. Herein, we report a method for covalent and orientation-selective immobilization of antibodies in designed cavities in 2D and 3D DNA origami structures. Two tris(NTA) modified strands are inserted into the cavity to form NTA-metal complexes with histidine clusters on the Fc domain. Subsequent covalent linkage to the antibody was achieved by coupling to lysines. Atomic force microscopy (AFM) and transmission electron microscopy (TEM) validated efficient antibody immobilization in the origami structures. The increased ability to control the orientation of antibodies in nanostructures and at surfaces has potential for directing the interactions of antibodies with targets and to provide more regular surface assemblies of antibodies.