Department of Physics, George Washington University, Washington, DC, USA.
Biophys J. 2013 Aug 20;105(4):984-92. doi: 10.1016/j.bpj.2013.07.004.
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.
多价阳离子导致 DNA 凝聚的物理起源仍未解决。在这里,我们报告了定量研究,研究了一种 DNA 凝聚离子(六氨合钴(3+),或 Co(3+)Hex)和一种非 DNA 凝聚离子(Mg(2+))如何在自发凝聚的 DNA 阵列的间隙空间中竞争。随着浴液中离子浓度的系统变化,通过原子发射光谱和 X 射线衍射分别确定 DNA 阵列的离子含量和 DNA-DNA 间距。为了获得定量见解,我们首先将实验测定的离子含量与基于非线性泊松-玻尔兹曼方程的精确数值计算的预测进行比较。此类计算显著低估了 Co(3+)Hex 离子的数量,这与非线性泊松-玻尔兹曼方法在描述多价阳离子方面的缺陷一致。随着 Mg(2+)浓度的增加,由于离子竞争削弱了 DNA-DNA 吸引力,Co(3+)Hex 凝聚的 DNA 阵列会膨胀并最终重新溶解。尽管 DNA-DNA 间距取决于浴液中 Mg(2+)和 Co(3+)Hex 的浓度,但观察到间距主要由 DNA 阵列的一个参数决定,即 Co(3+)Hex 中和的 DNA 电荷分数。还观察到,仅需 Co(3+)Hex 中和约 20%的 DNA 电荷即可实现自发 DNA 凝聚。然后,我们表明浴离子条件可以简化为一个变量,使用简单的离子结合模型,该模型能够合理地描述离子含量和 DNA-DNA 间距的变化。最后,我们讨论了对间隙离子和阳离子介导的 DNA-DNA 相互作用的性质的影响。