Multivalent Pattern Recognition Through Engineering of Spatial Tolerance in DNA-Based Nanomaterials

Strength in numbers, combining many weak interactions into an overall strong connection, is the fundamental principle of multivaleny. This concept has been exploiting for the engineering of super-selective cell-targeting materials, which generally display high number of flexible ligands to enhance the systems' avidity. Many biological processes, however, function through a temporal spatial organization of receptors in patterns, matching with a controlled number of ligands to create a specific interaction. In this low-valency regime, the mechanics e.g. rigidity of the ligand-presenting architecture plays a critical role in the selectivity of the multivalent complex. Exploiting the precision in spatial design inherent to DNA nanotechnology, we engineered a library of scaffolds to explore how valency, affinity, and rigidity control the balance of super-selective multivalent binding. Depending on the affinity between the ligand and receptor, a pattern-dependent binding behavior was achieved when spatial tolerance of ligands matches the spatial organization of the target. We label this new form of mechanics-controlled multivalent binding "multivalent pattern recognition" (MPR). The main parameter controlling MPR is the rigidity of the ligand, which controls the over spatial tolerance of binding. Our findings contribute to the rational design of selective targeting with nanomaterials.