Passivation and preferential attachment of biomolecules. Tunable affinity towards biomolecules is a highly desired property of surfaces. Here we demonstrate that polypeptoid brush monolayers are capable of tuning the affinity of surfaces towards DNA origami nanostructures (61 nm × 52 nm cuboid nanostructure with an aperture). Among the five polypeptoids, two polypeptoids are identified as good surface passivation molecules with either methoxyethyl or butyl side chains, while polypeptoids containing aromatic groups induce preferential attachment of DNA origami nanostructures on corresponding surfaces (Figure ). Previous strategies for surface passivation against DNA origami are commonly achieved with a hydrophobic trimethylsilyl layer produced by hexamethyldisilane (HMDS). The binding of DNA origami on surfaces is most commonly mediated through electrostatic interactions, using Mg 2+ as the electrostatic bridge between negatively charged DNA origami and negatively charged surfaces (e.g., Si, mica). Here, we discovered that the binding affinity of DNA origami is decoupled from surface hydrophilicity.