Ion Competition in Condensed DNA Arrays in the Attractive Regime

Abstract

Physical origin of DNA condensation by multivalent cations remains unsettled. Here, we report quantitative studies of how one DNA-condensing ion (Cobalt(3+) Hexammine, or Co(3+)Hex) and one nonDNA-condensing ion (Mg(2+)) compete within the interstitial space in spontaneously condensed DNA arrays. As the ion concentrations in the bath solution are systematically varied, the ion contents and DNA-DNA spacings of the DNA arrays are determined by atomic emission spectroscopy and x-ray diffraction, respectively. To gain quantitative insights, we first compare the experimentally determined ion contents with predictions from exact numerical calculations based on nonlinear Poisson-Boltzmann equations. Such calculations are shown to significantly underestimate the number of Co(3+)Hex ions, consistent with the deficiencies of nonlinear Poisson-Boltzmann approaches in describing multivalent cations. Upon increasing the concentration of Mg(2+), the Co(3+)Hex-condensed DNA array expands and eventually redissolves as a result of ion competition weakening DNA-DNA attraction. Although the DNA-DNA spacing depends on both Mg(2+) and Co(3+)Hex concentrations in the bath solution, it is observed that the spacing is largely determined by a single parameter of the DNA array, the fraction of DNA charges neutralized by Co(3+)Hex. It is also observed that only ∼20% DNA charge neutralization by Co(3+)Hex is necessary for spontaneous DNA condensation. We then show that the bath ion conditions can be reduced to one variable with a simplistic ion binding model, which is able to describe the variations of both ion contents and DNA-DNA spacings reasonably well. Finally, we discuss the implications on the nature of interstitial ions and cation-mediated DNA-DNA interactions.

Multi-shell model of ion-induced nucleic acid condensation

“…First, at the nearneutralizing conditions necessary for NA condensation, the fractions of CoHex ions in the "external" ion binding shells of the four NA duplexes correlate with measured condensation propensities of these duplexes [50]. Second, the "external" CoHex binding shells of NA molecules are the only shells that overlap substantially at the interaxial duplex separation corresponding to the separations observed in CoHex condensed (aggregated) DNA phases (about 28Å [16,59]).…”

“…In our estimations we use ∆X = ∆Y = (d−2a)/2 where d is inter-axial duplex separation and a is the radius of the NA duplex estimated as a = 11Å. At d = 28 A corresponding to duplex separation observed in CoHex condensed DNA phases [16,59], ∆X = ∆Y = 3Å -a half-width of the nucleic acid effective attraction energy well [51] at 5k B T above the minimum. For simplicity we use the same value for ∆Z (∆Z = 3Å), which describes the vertical misalignment of the ends of parallel duplexes in the hexagonal bundle.…”

Molecular dynamics simulations demonstrate the regulation of DNA‐DNA attraction by H4 histone tail acetylations and mutations

“…Notably, the most populated DNA-DNA distance for the H4N and H4W systems, 26 to 32 Å , corresponds to typical DNA-DNA separations reported in experimental studies of DNA condensation by multicationic ligands[76][77][78][79][80] (and references cited therein). However, the major features of the distribution are defined by the nature of the histone tail fragment and the peaks in the DNA-DNA distributions are separated by a substantial 15 Å (Figure 2B).…”

Many-body effect in ion binding to RNA

“…Therefore, RNA folding is sensitive to the property of the surrounding ions, such as the ion type, size, valence, and concentration. 4,[13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] Furthermore, RNA molecules can be highly dynamic. For a RNA in the unfolded and the intermediate states, RNA can sample an ensemble of conformations.…”