Engineering Lipid Membranes with Programmable DNA Nanostructures

Lipid and DNA are abundant biomolecules with critical functions in cells. The water‐insoluble, amphipathic lipid molecules are best known for their roles in energy storage (e.g., as triglyceride), signaling (e.g., as sphingolipid), and compartmentalization (e.g., by forming membrane‐enclosed bodies). The soluble, highly negatively charged DNA, which stores the cells' genetic information, has proven to be an excellent material for constructing programmable nanostructures in vitro thanks to its self‐assembling capabilities. These two seemingly distant molecules make contact within cell nuclei, often via lipidated proteins, with proposed functions of modulating chromatin structures. Carefully formulated lipid/DNA complexes are promising reagents for gene therapy. The past few years have seen an emerging research field of interfacing DNA nanostructures with lipid membranes, with an overarching goal of generating DNA/lipid hybrid materials that possess novel and controllable structure, dynamics, and function. An arsenal of DNA‐based tools has been created to coat, mold, deform, and penetrate lipid bilayers, affording the ability to manipulate membranes with nanoscopic precision. These membrane engineering methods not only enable quantitative biophysical studies, but also open new opportunities in synthetic biology (e.g., artificial cells) and therapeutics (e.g., drug delivery).