DNA Nanostructures Interacting with Lipid Bilayer Membranes

Abstract

CONSPECTUS: DNA has been previously shown to be useful as a material for the fabrication of static nanoscale objects, and also for the realization of dynamic molecular devices and machines. In many cases, nucleic acid assemblies directly mimic biological structures, for example, cytoskeletal filaments, enzyme scaffolds, or molecular motors, and many of the applications envisioned for such structures involve the study or imitation of biological processes, and even the interaction with living cells and organisms. An essential feature of biological systems is their elaborate structural organization and compartmentalization, and this most often involves membranous structures that are formed by dynamic assemblies of lipid molecules. Imitation of or interaction with biological systems using the tools of DNA nanotechnology thus ultimately and necessarily also involves interactions with lipid membrane structures, and thus the creation of DNA-lipid hybrid assemblies. Due to their differing chemical nature, however, highly charged nucleic acids and amphiphilic lipids do not seem the best match for the construction of such systems, and in fact they are rarely found in nature. In recent years, however, a large variety of lipid-interacting DNA conjugates were developed, which are now increasingly being applied also for the realization of DNA nanostructures interacting with lipid bilayer membranes. In this Account, we will present the current state of this emerging class of nanosystems. After a brief overview of the basic biophysical and biochemical properties of lipids and lipid bilayer membranes, we will discuss how DNA molecules can interact with lipid membranes through electrostatic interactions or via covalent modification with hydrophobic moieties. We will then show how such DNA-lipid interactions have been utilized for the realization of DNA nanostructures attached to or embedded within lipid bilayer membranes. Under certain conditions, DNA nanostructures remain mobile on membranes and can dynamically associate into higher order complexes. Hydrophobic modification of DNA nanostructures can further result in intra- or intermolecular aggregation, which can also be utilized as a structural switching mechanism. Appropriate design and chemical modification even allows insertion of DNA nanostructures into lipid bilayer membranes, resulting in artificial ion channel mimics made from DNA. Interactions of DNA nanodevices with living cells also involve interactions with membrane structures. DNA-based nanostructures can be directed to cell surfaces via antibody-antigen interactions, and their cellular uptake can be stimulated by modification with appropriate receptor ligands. In the future, membrane-embedded DNA nanostructures are expected to find application in diverse areas ranging from basic biological research over nanotechnology to synthetic biology.

Terminal lipophilization of a unique DNA dodecamer by various nucleolipid headgroups: Their incorporation into artificial lipid bilayers and hydrodynamic properties

“…The studies described in this manuscript complement the research of various scientific groups whose work is focused on the formation of complex nanoarchitectures [33–34], the interaction of such nanostructures with lipid membranes [35–38], as well as the optimization of the in vivo delivery of lipophilic siRNA [10–12] (e.g., by DNA trafficking [7]).…”

Lipid Exchange Envelope Penetration (LEEP) of Nanoparticles for Plant Engineering: A Universal Localization Mechanism

“…45 They further found that at suitable salt concentrations, charged polymers (polyethyleneamine) are adsorbed onto the surface of DMPC vesicles. Similarly, Langecker and co-workers 46 specifically studied DNA−lipid interactions and how DNA nanostructures can either remain mobile on membranes or can be embedded within lipid bilayers. Interestingly, Bo and coworkers 47 also found via fluorescence and calorimetry methods that the local phase state of phospholipid bilayers can be switched by binding of charged nanoparticles such that they alter the tilt angle of the phosphocholine.…”

Supramolecular Langmuir monolayers and multilayered vesicles of self-assembling DNA–lipid surface structures and their further implications in polyelectrolyte-based cell transfections

“…The importance of the topic was emphasized in a recent review (Langecker et al 2014). For this, a synthetic system currently developed for transfer of therapeutic nucleic acids into target cells using a synthetic DNA supramolecular assembly is presented.…”