Docking of Antibodies into the Cavities of DNA Origami Structures

Abstract 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 of immobilized antibodies on surfaces is very limited. Herein, we report a method for the 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 lysine residues. Atomic force microscopy (AFM) and transmission electron microscopy (TEM) confirmed the efficient immobilization of the antibodies in the origami structures. This increased control over the orientation of antibodies in nanostructures and on surfaces has the potential to direct the interactions between antibodies and targets and to provide more regular surface assemblies of antibodies.