Two‐Dimensional Supramolecular Polymerization of DNA Amphiphiles is Driven by Sequence‐Dependent DNA‐Chromophore Interactions

Two‐dimensional (2D) assemblies of water‐soluble block copolymers have been limited by a dearth of systematic studies that relate polymer structure to pathway mechanism and supramolecular morphology. Here, we employ sequence‐defined triblock DNA amphiphiles for the supramolecular polymerization of free‐standing DNA nanosheets in water. Our systematic modulation of amphiphile sequence shows the alkyl chain core forming a cell membrane‐like structure and the distal π‐stacking chromophore block folding back to interact with the hydrophilic DNA block on the nanosheet surface. This interaction is crucial to sheet formation, marked by a chiral “signature”, and sensitive to DNA sequence, where nanosheets form with a mixed sequence, but not with a homogeneous poly(thymine) sequence. This work opens the possibility of forming well‐ordered, bilayer‐like assemblies using a single DNA amphiphile for applications in cell sensing, nucleic acid therapeutic delivery and enzyme arrays. Supramolecular DNA nanosheets resembling bilayer membranes are obtained from the self‐assembly of triblock DNA amphiphiles incorporating Cy3 chromophores. The hydrophobic chromophores are found to interact in a sequence‐dependent manner with the hydrophilic DNA on the sheet surface, generating a chiral “signature” only upon formation of the thermodynamically stable nanosheet morphology.