Emerging applications at the interface of DNA nanotechnology and cellular membranes: Perspectives from biology, engineering, and physics

DNA nanotechnology has proven exceptionally apt at probing and manipulating biological environments as it can create nanostructures of almost arbitrary shape that permit countless types of modifications, all while being inherently biocompatible. Emergent areas of particular interest are applications involving cellular membranes, but to fully explore the range of possibilities requires interdisciplinary knowledge of DNA nanotechnology, cell and membrane biology, and biophysics. In this review, we aim for a concise introduction to the intersection of these three fields. After briefly revisiting DNA nanotechnology, as well as the biological and mechanical properties of lipid bilayers and cellular membranes, we summarize strategies to mediate interactions between membranes and DNA nanostructures, with a focus on programmed delivery onto, into, and through lipid membranes. We also highlight emerging applications, including membrane sculpting, multicell self-assembly, spatial arrangement and organization of ligands and proteins, biomechanical sensing, synthetic DNA nanopores, biological imaging, and biomelecular sensing. Many critical but exciting challenges lie ahead, and we outline what strikes us as promising directions when translating DNA nanostructures for future in vitro and in vivo membrane applications.