Topology-preserving modifications of C-star motifs C-stars are simple amphiphilic motifs based on DNA nanostars, composed of 4 coreforming oligonucleotides and 4 cholesterolfunctionalized strands (Fig. ). Slow cooling of a stoichiometric mixture of these components leads to the self-assembly of macroscopic single crystals in a straightforward one-pot re-action (Fig. ). In contrast to approaches reliant on Watson-Crick and/or stacking interactions alone, where a successful selfassembly requires the fine tuning of the building block geometry with atomic resolution, in Cstar frameworks long-range order emerges from the frustrated phase separation between the hydrophobic cholesterol and the hydrophilic DNA. This mechanism is controlled uniquely by the topology and symmetry of the flexible nanostar motif, which makes C-star self-assembly potentially robust against substantial design changes that preserve these features.