DNA condensation by multivalent cations

Abstract

In the presence of multivalent cations, high molecular weight DNA undergoes a dramatic condensation to a compact, usually highly ordered toroidal structure. This review begins with an overview of DNA condensation:condensing agents, morphology, kinetics and reversibility, and the minimum size required to form orderly condensates. It then summarizes the statistical mechanics of the collapse of stiff polymers, which shows why DNA condensation is abrupt and why toroids are favored structures. Various ways to estimate or measure intermolecular forces in DNA condensation are discussed, all of them agreeing that the free energy change per base pair is very small, on the order of 1% of thermal energy. Experimental evidence is surveyed showing that DNA condensation occurs when about 90% of its charge is neutralized by counterions. The various intermolecular forces whose interplay gives rise to DNA condensation are then reviewed. The entropy loss upon collapse of the expanded wormlike coil costs free energy, and stiffness sets limits on tight curvature. However, the dominant contributions seem to come from ions and water. Electrostatic repulsions must be overcome by high salt concentrations or by the correlated fluctuations of territorially bound multivalent cations. Hydration must be adjusted to allow a cooperative accommodation of the water structure surrounding surface groups on the DNA helices as they approach. Undulations of the DNA in its confined surroundings extend the range of the electrostatic forces. The condensing ions may also subtly modify the local structure of the double helix.

Spermine Condenses DNA, but Not RNA Duplexes

“…The DNA duplexes precipitate completely when the spermine concentration is 1 mM, roughly half the concentration of phosphate in the duplexes. This agrees with previous work showing that a significant amount of spermine is required to precipitate DNA (13). Prior experiments using CoHex suggest that an even higher concentration is required to completely draw the DNA out of solution (19).…”

“…The duplexes were solvated with 16,880 TIP3P water molecules and a neutralizing amount of spermine (12 molecules). This amount is relevant to compare with experimental measurements of duplex condensation, which begins when~90% of the phosphate charge is neutralized by the counterions (13). An initial 2000-step water minimization was followed by a 0.5 ns equilibration time in a canonical NVT ensemble and another 0.5 ns in an isothermal-isobaric (NPT) ensemble using 1 fs time steps.…”

“…With so many spermine molecules associating with RNA, it is important to consider the possibility of cation-induced condensation, in which small amounts of multivalent cations cause highly charged, ordinarily self-repelling nucleic acids to adopt a compact state occupying only a fraction of the volume available to them (12)(13)(14). Previous studies of spermine-induced RNA condensation had a limited scope but showed that spermine can condense RNAs with nonphysiological sequences or under nonphysiological experimental conditions, e.g., long duplex poly(rA):poly(rU) (15), tRNA at nonphysiological pHs (16), and viral RNA in the complete absence of other salts (17).…”

“…This sequence favors duplex formation over stem loops in the individual strands and has a high melting temperature (61 C as calculated with OligoCalc (24)). We compared the experimental results with all-atom molecular-dynamics (MD) simulations to develop a model in which the distribution of bound CoHex ions relates to the condensation propensity: nucleic acids with more CoHex bound in the external binding shell (12)(13)(14)(15)(16) Å from the helical axis) condense most readily, whereas those with more ions bound to the internal shell (7-12 Å from the helical axis) resist condensation (23,25). Although these studies produced interesting experimental findings, they were not biological.…”

General electrokinetic model for concentrated suspensions in aqueous electrolyte solutions: Electrophoretic mobility and electrical conductivity in static electric fields

“…In fact, it has outstanding effects in the general electrostatics of soft matter, affecting the stability of colloids [42][43], or the self-assembly of biomolecules [44], as well as the compaction of genetic material [45]. The phenomenon also occurs in pure salt-free or low-salt regimes at finite volume fractions [46], and it has provided explanation to such findings as the independence of electrokinetic properties like electrophoretic mobility with particle charge [13][14][15]19], or the presence of a relaxation process linked to this condensate region in radiofrequency electric fields [23].…”