Programmable DNA shell scaffolds for directional membrane budding

Abstract

Abstract In the pursuit of replicating biological processes at the nanoscale, controlling cellular membrane dynamics has emerged as a key area of interest. Here, we report a system mimicking virus assembly to control directional membrane budding. We employ three-dimensional DNA origami techniques to construct cholesterol-modified triangles that self-assemble into polyhedral shells on lipid vesicles, resulting in gradual curvature induction, bud formation, and spontaneous neck scission. Strategic positioning of cholesterols on the triangle surface provides control over the directionality of bud growth and yields daughter vesicles with DNA endo- or exoskeletons reminiscent of clathrin-coated vesicles. This process occurs with rapid kinetics and across various lipid compositions. When combined into a two-step process, nested bivesicular objects with DNA shells encapsulated between lipid vesicles could be produced. Our work replicates key aspects of natural endocytic and exocytic pathways, opening new avenues for exploring membrane mechanics and applications in targeted drug delivery and synthetic biology.