Interplay of ion binding and attraction in DNA condensed by multivalent cations

We have measured forces generated by multivalent cation-induced DNA condensation using single-molecule magnetic tweezers. In the presence of cobalt hexammine, spermidine, or spermine, stretched DNA exhibits an abrupt configurational change from extended to condensed. This occurs at a well-defined condensation force that is nearly equal to the condensation free energy per unit length. The multivalent cation concentration dependence for this condensation force gives the apparent number of multivalent cations that bind DNA upon condensation. The measurements show that the lower critical concentration for cobalt hexammine as compared to spermidine is due to a difference in ion binding, not a difference in the electrostatic energy of the condensed state as previously thought. We also show that the resolubilization of condensed DNA can be described using a traditional Manning–Oosawa cation adsorption model, provided that cation–anion pairing at high electrolyte concentrations is taken into account. Neither overcharging nor significant alterations in the condensed state are required to describe the resolubilization of condensed DNA. The same model also describes the spermidine3+/Na+ phase diagram measured previously.

[1]  S. Smith,et al.  Ionic effects on the elasticity of single DNA molecules. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[2]  K. Downing,et al.  Cryoelectron microscopy of λ phage DNA condensates in vitreous ice: The fine structure of DNA toroids , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[3]  D. Durand,et al.  Interhelical spacing in liquid crystalline spermine and spermidine-DNA precipitates. , 2005, Biophysical journal.

[4]  I. Rouzina,et al.  Thermodynamics of DNA binding and condensation: isothermal titration calorimetry and electrostatic mechanism. , 2000, Journal of molecular biology.

[5]  N. Hud,et al.  Controlling the size of nanoscale toroidal DNA condensates with static curvature and ionic strength , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[6]  M. Olvera de la Cruz,et al.  Precipitation of DNA by polyamines: a polyelectrolyte behavior. , 1998, Biophysical journal.

[7]  G. Plum,et al.  Equilibrium dialysis study of binding of hexammine cobalt(III) to DNA. , 1988, Biopolymers.

[8]  R. Golestanian,et al.  Conformational instability of rodlike polyelectrolytes due to counterion fluctuations. , 2002, Physical review. E, Statistical, nonlinear, and soft matter physics.

[9]  Qiuwei Xu,et al.  Hexaamminecobalt(III) binding environments on double‐helical DNA , 1992, Biopolymers.

[10]  K. Besteman,et al.  Charge inversion accompanies DNA condensation by multivalent ions , 2007 .

[11]  Darrin M. York,et al.  The contribution of phosphate–phosphate repulsions to the free energy of DNA bending , 2005, Nucleic acids research.

[12]  V A Parsegian,et al.  Direct measurement of the intermolecular forces between counterion-condensed DNA double helices. Evidence for long range attractive hydration forces. , 1992, Biophysical journal.

[13]  F. Solis.  Phase diagram of dilute polyelectrolytes: Collapse and redissolution by association of counterions and co-ions , 2002, cond-mat/0204591.

[14]  M. Sano,et al.  Elastic response of single DNA molecules exhibits a reentrant collapsing transition. , 2003, Physical review letters.

[15]  Cees Dekker,et al.  Direct force measurements on DNA in a solid-state nanopore , 2006 .

[16]  G. S. Manning.  On the application of polyelectrolyte “limiting laws” to the helix‐coil transition of DNA. I. Excess univalent cations , 1972, Biopolymers.

[17]  V. Bloomfield,et al.  Macroion Attraction Due to Electrostatic Correlation between Screening Counterions. 1. Mobile Surface-Adsorbed Ions and Diffuse Ion Cloud , 1996 .

[18]  K. Besteman,et al.  Role of tension and twist in single-molecule DNA condensation. , 2007, Physical review letters.

[19]  G. S. Manning.  On the Application of Polyelectrolyte “Limiting Laws” to the Helix‐Coil Transition of DNA. II. The Effect of Mg++ Counterions , 1972, Biopolymers.

[20]  Jay X. Tang,et al.  Metal ion-induced lateral aggregation of filamentous viruses fd and M13. , 2002, Biophysical journal.

[21]  N. Hud,et al.  Toroidal DNA condensates: unraveling the fine structure and the role of nucleation in determining size. , 2005, Annual review of biophysics and biomolecular structure.

[22]  R. W. Wilson,et al.  Comparison of polyelectrolyte theories of the binding of cations to DNA. , 1980, Biophysical journal.

[23]  B. Shklovskii,et al.  The pulling force of a single DNA molecule condensed by spermidine , 2003, cond-mat/0310321.

[24]  G. S. Manning.  The molecular theory of polyelectrolyte solutions with applications to the electrostatic properties of polynucleotides , 1978, Quarterly Reviews of Biophysics.

[25]  S. Brasilès,et al.  Effect of spermine and DNase on DNA release from bacteriophage T5 , 2005, The European physical journal. E, Soft matter.

[26]  M. O. D. L. Cruz,et al.  Precipitation of highly charged polyelectrolyte solutions in the presence of multivalent salts , 1995 .

[27]  M. Record.  Effects of Na+ and Mg++ ions on the helix–coil transition of DNA , 1975 .

[28]  R. W. Wilson,et al.  Counterion-induced condesation of deoxyribonucleic acid. a light-scattering study. , 1979, Biochemistry.

[29]  Jie Yang,et al.  Incomplete ion dissociation underlies the weakened attraction between DNA helices at high spermidine concentrations. , 2005, Biophysical journal.

[30]  I. Rouzina,et al.  Reentrant condensation of DNA induced by multivalent counterions , 1999, cond-mat/9908428.

[31]  G. H. Nancollas,et al.  Spectrophotometric investigation of some complex cobaltic chloro, bromo, iodo, and azide ion-pairs , 1953 .

[32]  Michelle D. Wang,et al.  Stretching of single collapsed DNA molecules. , 2000, Biophysical journal.

[33]  Boris I Shklovskii,et al.  Colloquium: The physics of charge inversion in chemical and biological systems , 2002 .

[34]  D. Durand,et al.  DNA mesophases induced by spermidine: structural properties and biological implications. , 1996, Biophysical journal.

[35]  A Leforestier,et al.  Spermine-induced aggregation of DNA, nucleosome, and chromatin. , 1999, Biophysical journal.

[36]  Flexible linear polyelectrolytes in multivalent salt solutions: Solubility conditions , 2000, cond-mat/0003320.

[37]  M. Record,et al.  Equilibrium dialysis studies of polyamine binding to DNA , 1982, Biopolymers.

[38]  J. Pelta,et al.  DNA Aggregation Induced by Polyamines and Cobalthexamine (*) , 1996, The Journal of Biological Chemistry.

[39]  Tamar Schlick,et al.  Role of histone tails in chromatin folding revealed by a mesoscopic oligonucleosome model , 2006, Proceedings of the National Academy of Sciences.