Programmable DNA shell scaffolds for directional membrane budding

Abstract

AbstractIn the pursuit of understanding and replicating biological processes at the nanoscale, controlling cellular membrane dynamics has emerged as a key area of interest. Here, we report a system capable of controlling directional membrane budding through a mechanism mimicking virus assembly on a lipid membrane. We employed three-dimensional DNA origami techniques to construct icosahedral shells that self-assemble and interact with the lipid membranes of giant vesicles via cholesterol moieties. The membrane-constrained assembly of shells results in the programmable formation of DNA-shell-coated vesicles or vesicle-coated DNA shells, effectively demonstrating membrane curvature induction and spontaneous neck scission. We further show that these processes can be combined into a 2-step budding reaction, giving rise to nested bivesicular objects with DNA shells encapsulated between two lipid vesicles. Our findings replicate key aspects of natural endocytic and exocytic pathways, and open new avenues for the exploration of membrane mechanics and for applications in targeted drug delivery and synthetic biology.