The Role of Structural Enthalpy in Spherical Nucleic Acid Hybridization

DNA hybridization onto DNA-functionalized nanoparticle surfaces (e.g., in the form of a spherical nucleic acid (SNA)) is known to be enhanced relative to hybridization free in solution. This chapter provides insight into one of the most important and enabling properties of SNAs and will inform the design of materials that rely on the thermodynamics of hybridization onto DNA-functionalized surfaces, including diagnostic probes and therapeutic agents. SNAs have become important entities in the development of medical diagnostic probes, intracellular small-molecule detection agents, RNA tracking agents, and building blocks for colloidal crystal engineering. Their unique properties, which are highly differentiated from linear structures, make them very attractive for such uses. To determine the entropies and enthalpies of binding, concentration-dependent fluorescence hybridization experiments are performed. The van’t Hoff analysis assumes that DNA hybridization proceeds in the dilute limit in a two-state manner and that the enthalpy of this process is independent of temperature.