What Controls the Hybridization Thermodynamics of Spherical Nucleic Acids?*

The hybridization of free oligonucleotides to densely packed, oriented arrays of DNA modifying the surfaces of spherical nucleic acid (SNA)–gold nanoparticle conjugates occurs with negative cooperativity; that is, each binding event destabilizes subsequent binding events. DNA hybridization is thus an ever-changing function of the number of strands already hybridized to the particle. This chapter quantifies the thermodynamics of binding as a function of the number of pre-hybridized strands. This analysis provides important fundamental insight into the enthalpic and entropic consequences of packing charged DNA strands into a dense monolayer and reveals that SNA binding is regulated by electrostatic effects and collective conformational changes that are analogous to the phenomenon of allostery observed in many regulatory proteins. The chapter draws several important lessons regarding the thermodynamics of oligonucleotide hybridization to SNA–gold nanoparticles conjugates.