Self-assembled DNA nanostructures for distance dependent multivalent ligand-protein binding

摘要

An interesting goal of nanotechnology is to assemble biomolecules to display multivalent interactions, which are characterized by simultaneous binding of multiple ligands on one biological entity to multiple receptors on another with high avidity. Various approaches have been developed to engineer multivalency by linking multiple ligands together^-. However, the effects of well-controlled inter-ligand distances on multivalency are less understood. Recent progress in self-assembling DNA tile-based nanostructures with spatial and sequence addressability^- has made deterministic positioning of different molecular species possible^,-. Here we show that distance-dependent multivalent binding effects can be systematically investigated by incorporating multiple affinity ligands into DNA nanostructures with precise nanometer spatial control. Using atomic force microscopy (AFM), we demonstrate direct visualization of high avidity bivalent ligands being used as pincers to capture and display protein molecules on a nanoarray. Our results set forth a path for constructing spatial combinatorics at the nanometer scale.