Functional and Biomimetic DNA Nanostructures on Lipid Membranes

Sophisticated and dynamic membrane-anchored DNA nanostructures were developed to mimic a variety of membrane proteins, which play crucial roles in cellular functions. DNA biomimetic constructions bound on membranes are capable of modulating the morphologies, physical properties, and functions of lipid membranes, via mobility on membranes and/or inherent architectural features. This inspired young field of DNA-lipid-based nanobiomimetic systems is on the foundation of DNA nanotechnology. In this review, we highlight key successes in the development of structural DNA nanotechnology and demonstrate some typical static and dynamic complex DNA nanostructures first. Then, we discuss the biophysical properties of lipid membranes. Primary approaches are shown to attach hydrophilic DNA to hydrophobic lipid membranes. With appropriate designs, membrane-floating DNA nanostructures assemble and disassemble on membranes, modulated by  external stimuluses. The aggregation of DNA nanostructures could influence the physical properties of lipid membranes. We also summarize artificial nanochannels made of DNA, analogous to transmembrane proteins. Transformations of DNA nanopores might be achieved under certain conditions and realize the transport of small molecules across membranes. Next, we focus on membrane-shaping functions of membrane-anchored DNA nanostructures. Curvature of the membrane is closely related to the rich diversity of cellular functions. Mimicking membrane-sculpting proteins, such as BAR family domains and SNARE proteins etc., DNA biomimetic nanostructures induce the transformations of lipid membranes and modulate membrane adhesion and membrane fusion processes. Although recent studies in DNA nanostructure-lipid membrane biomimetic nanosystems have made great progress, this field is still facing many challenges. In the future, the designs of more elaborated DNA architectures will be explored. Sophisticated dynamic DNA nanostructures inspired by natural membrane machines will be driven by the synergistic effect of multiple interactions, including hydrophobic force, electrostatic force, and ligand-receptor interactions by chemical modifications on bases, to expand their applications in vivo from model membrane to cell membrane to karyotheca.