Chemistry has the power to endow supramolecular nanostructures with new biomedically relevant functions. Here it is reported that DNA nanostructures modified with cholesterol tags disrupt bacterial membranes to cause microbial cell death. The lipidated DNA nanostructures bind more readily to cholesterol-free bacterial membranes than to cholesterol-rich, eukaryotic membranes. These highly negatively charged, lipidated DNA nanostructures cause bacterial cell death by rupturing membranes. Strikingly, killing is mediated by clusters of barrel-shaped nanostructures that adhere to the membrane without the involvement of expected bilayer-puncturing barrels. These DNA nanomaterials may inspire the development of polymeric or small-molecule antibacterial agents that mimic the principles of selective binding and rupturing to help combat antimicrobial resistance.

Lipidated DNA Nanostructures Target and Rupture Bacterial Membranes