Here we demonstrate how a platform based on newly introduced amphiphilic DNA nanostructures, dubbed C-stars, can overcome the aforementioned limitations, offering a one-pot route for the formation of highly porous, bulk crystalline mesophases able to robustly support changes in structure and functionality. Rather than depending on the fine geometrical details of the building blocks, the crystal structure of C-star frameworks is prescribed solely by the topology and symmetry of the amphiphilic DNA motifs. We exploit this unique feature to produce a range of topology-preserving Cstar designs forming a variety of frameworks with distinct structure and functionalities that nevertheless share the same crystal geometry. We can precisely and continuously tune lattice parameter and framework mesh size, which allows us to control the partitioning of a range of macromolecules. Building blocks tagged with a ligand form frameworks that can specifically and reversibly entrap a target protein, while the use of C-stars modified with a responsive DNA motif leads to triggered disassembly of the frameworks. Furthermore, the resilience of the self-assembly mechanism of C-stars makes crystallization robust to low-ionic strength conditions and to the use of unpurified components.