Physical and biochemical insights on DNA structures in artificial and living systems

CONSPECTUS: Highly specific DNA base-pairing is the basis for both fulfilling its genetic role and constructing novel nanostructures and hybrid conjugates with inorganic nanomaterials (NMs). There exist many remarkable differences in the physical properties of single-stranded (ss) and double-stranded (ds) DNA, which play important roles in regulation of biological processes in nature. Rapid advances in nanoscience and nanotechnology pose new questions on how DNA and DNA structures interact with inorganic nanomaterials or cells and animals, which should be important for their biological and biomedical applications. In this Account, we intend to provide an overview on many facets of DNA and DNA structures in artificial and living systems, with the focus on their properties and functions at the interfaces of inorganic nanomaterials and biological systems. ssDNA, dsDNA, and DNA nanostructures interact with NMs in different ways. In particular, gold nanoparticles and graphene oxide exhibit strikingly different affinity toward ssDNA and dsDNA. Such binding differences can be coupled with optical properties of NMs. For example, DNA hybridization can effectively modulate the plasmonic and catalytic properties of gold nanoparticles. By exploitation of these interactions, there have been many ways for sensitive transduction of biomolecular recognition for various sensing applications. Alternatively, modulation of the properties of DNA and DNA structures with NMs has led to new tools for genetic analysis including genotyping and haplotyping. Self-assembled DNA nanostructures have emerged as a new type of NMs with pure biomolecules. These nanostructures can be designed in one, two, or three dimensions with various sizes, shapes, and geometries. They also have characteristics of uniform size, precise addressability, excellent water solubility, and biocompatibility. These nanostructures provide a new toolbox for biophysical studies with unparalleled advantages, for example, NMR-based protein structure determination and single-molecule studies. Also importantly, DNA nanostructures have proven highly useful in various applications including biological detection, bioreactors, and nanomedicine. In particular, DNA nanostructures exhibit high cellular permeability, a property that is not available for ssDNA and dsDNA, which is required for their drug delivery applications. DNA and DNA structures can also form hybrids with inorganic NMs. Notably, DNA anchored at the interface of inorganic NMs behaves differently from that at the macroscopic interface. Several types of DNA-NM conjugates have exerted beneficial effects for bioassays and in vitro translation of proteins. Even more interestingly, hybrid nanoconjugates demonstrate distinct properties under the context of biological systems such as cultured cells or animal models. These unprecedented properties not only arouse great interest in studying such interfaces but also open new opportunities for numerous applications in artificial and living systems.