Vesicle-templated self-assembly of freestanding multi-μm DNA shells

In the quest to create increasingly complex synthetic cell-mimicking systems, a wide range of DNA nanostructures have been developed to coat, permeabilize, sculpt, or otherwise functionalize lipid vesicles. In a complementary strategy, DNA architectures have been used as scaffolds to direct the growth of lipid membrane vesicles. However, no systematic attempts have yet been made to invert this strategy and use lipid vesicles as scaffolds for extended DNA super-assemblies, thereby realizing freestanding, membrane-mimicking DNA shells. Here we introduce a simple and broadly applicable method to implement this concept: DNA shells are first assembled on giant unilamellar vesicles and then liberated by surfactant-mediated liposome removal. We demonstrate the approach with two distinct classes of DNA tectons: a complex barrel-shaped DNA origami with programmable inter-subunit interactions, and a simple nanostar-inspired motif composed of only eleven oligonucleotides. The success of both strategies underscores the generality of our approach and the feasibility of creating shell-like compartments from different DNA architectures. This method enables the construction of tunable, DNA-only containers spanning the size range of eukaryotic cells, offering a fundamentally new type of compartmentalization for bottom-up synthetic biology.