title: Cation-Anion Interactions within the Nucleic Acid Ion Atmosphere Revealed by Ion Counting.
abstract: The ion atmosphere is a critical structural, dynamic, and energetic component of nucleic acids that profoundly affects their interactions with proteins and ligands. Experimental methods that "count" the number of ions thermodynamically associated with the ion atmosphere allow dissection of energetic properties of the ion atmosphere, and thus provide direct comparison to theoretical results. Previous experiments have focused primarily on the cations that are attracted to nucleic acid polyanions, but have also showed that anions are excluded from the ion atmosphere. Herein, we have systematically explored the properties of anion exclusion, testing the zeroth-order model that anions of different identity are equally excluded due to electrostatic repulsion. Using a series of monovalent salts, we find, surprisingly, that the extent of anion exclusion and cation inclusion significantly depends on salt identity. The differences are prominent at higher concentrations and mirror trends in mean activity coefficients of the electrolyte solutions. Salts with lower activity coefficients exhibit greater accumulation of both cations and anions within the ion atmosphere, strongly suggesting that cation-anion correlation effects are present in the ion atmosphere and need to be accounted for to understand electrostatic interactions of nucleic acids. To test whether the effects of cation-anion correlations extend to nucleic acid kinetics and thermodynamics, we followed the folding of P4-P6, a domain of the Tetrahymena group I ribozyme, via single-molecule fluorescence resonance energy transfer in solutions with different salts. Solutions of identical concentration but lower activity gave slower and less favorable folding. Our results reveal hitherto unknown properties of the ion atmosphere and suggest possible roles of oriented ion pairs or anion-bridged cations in the ion atmosphere for electrolyte solutions of salts with reduced activity. Consideration of these new results leads to a reevaluation of the strengths and limitations of Poisson-Boltzmann theory and highlights the need for next-generation atomic-level models of the ion atmosphere.
authors.affiliation: Department of Biochemistry, Stanford University , Stanford, California 94305, United States.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Gebala
authors.affiliation: BioMaPS Institute for Quantitative Biology and Department of Chemistry and Chemical Biology, Rutgers University , Piscataway, New Jersey 08854, United States.
authors.forename: George M
authors.initials: GM
authors.lastname: Giambaşu
authors.affiliation: Department of Physics, Nanosystems Initiative Munich, and Center for Nanoscience, Ludwig Maximilian University of Munich , 80799 Munich, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Lipfert
authors.affiliation: Department of Biochemistry, Stanford University , Stanford, California 94305, United States.
authors.forename: Namita
authors.initials: N
authors.lastname: Bisaria
authors.affiliation: Department of Chemical Engineering, Stanford University , Stanford, California 94305, United States.
authors.forename: Steve
authors.initials: S
authors.lastname: Bonilla
authors.affiliation: School of Earth, Energy and Environment Sciences, Stanford University , Stanford, California 94305, United States.
authors.forename: Guangchao
authors.initials: G
authors.lastname: Li
authors.affiliation: BioMaPS Institute for Quantitative Biology and Department of Chemistry and Chemical Biology, Rutgers University , Piscataway, New Jersey 08854, United States.
authors.forename: Darrin M
authors.initials: DM
authors.lastname: York
authors.affiliation: Department of Biochemistry, Stanford University , Stanford, California 94305, United States.|Department of Chemistry, Stanford University , Stanford, California 94305, United States.
authors.forename: Daniel
authors.initials: D
authors.lastname: Herschlag
mesh_terms: D000838:Anions; D002412:Cations; D013058:Mass Spectrometry; D009696:Nucleic Acids / Q000737:chemistry*
chemical_list: D000838:Anions; D002412:Cations; D009696:Nucleic Acids