DNA Origami – Lipid Membrane Interactions Controlled by Nanoscale Sterics

Abstract DNA nanostructures designed to interact with bilayer membranes are of fundamental interest as they mimic biological cytoskeletons and other membrane‐associated proteins for applications in synthetic biology, biosensing, and biological research. Yet, there is limited insight into how the binary interactions are influenced by steric effects produced by 3D geometries of DNA structures and membranes. This work uses a 3D DNA nanostructure with membrane anchors in four different steric environments to elucidate the interaction with membrane vesicles of varying sizes and different local bilayer morphology. It is found that interactions are significantly affected by the steric environments of the anchors ‐often against predicted accessibility‐ as well as local nanoscale morphology of bilayers rather than on the usually considered global vesicle size. Furthermore, anchor‐mediated bilayer interactions are co‐controlled by weak contacts with non‐lipidated DNA regions, as showcased by pioneering size discrimination between 50 and 200 nm vesicles. This study extends DNA nanotechnology to controlled bilayer interactions and can facilitate the design of nanodevices for vesicle‐based diagnostics, biosensing, and protocells.