Translational Entropy-Driven Competitive and Additive Effects on DNA Higher-Order Structure via Ion Exchange Between Cations of Different Valencies

DNA conformational transitions in aqueous environments are strongly influenced by electrostatic interactions with surrounding cations. This review/perspective article summarizes the experimental findings reported during the last decade on the competitive/cooperative effects of cations with different valencies on DNA conformational behavior. Recent experimental studies based on single DNA observations have shown that divalent cations, such as Mg(2+) and Ca(2+), can inhibit DNA compaction induced by the trivalent cation spermidine (SPD(3+)), revealing that the effects of coexisting cations are not simply additive. Such competitive behavior cannot be adequately explained within the conventional Debye-Hückel framework, which predicts always additive electrostatic screening contributions from cations of different valencies. To elucidate the underlying mechanism of competitive effects, a theoretical framework has been proposed by extending the framework of current counterion condensation theory, which incorporates changes in translational entropy arising from the ion-exchange process between monovalent counterions and divalent or trivalent cations interacting with DNA as a highly negatively charged polyelectrolyte. In the theoretical framework, the increase in translational entropy arises from the ion exchange process between monovalent counterions and trivalent cations in the absence of divalent cations, whereas the presence of divalent cations diminishes the entropic gain associated with this exchange. By interpreting the recent experimental findings through the aid of the development of theoretical modeling, this review/perspective article provides a coherent insight on how coexisting multiple cations regulate DNA conformation.