A broad range of manufactured products and biological fluids are colliods. The ability to understand and control the processes (of scientific, technological and industrial interest) in which such colloids are involved relies upon a precise knowledge of the electrical double layer. The traditional approach to describing this ion cloud around colloidal particles has been the Gouy-Chapman model developed on the basis of the Poisson-Boltzmann equation. Since the early 1980s, however, more sophisticated theoretical treatments have revealed both quantitative and qualitative deficiencies in the Poisson-Boltzmann theory, particularly at high ionic strengths and/or high surface charge densities. This review deals with these novel approaches, which are mostly computer simulations and approximate integral equation theories based on the so-called primitive model. Special attention is paid to phenomena that cannot be accounted for by the classic theory as a result of neglecting ion size correlations, such as overcharging, namely, the counterion concentration in the immediate neighborhood of the surface is so large that the particle surface is overcompensated. Other illustrative examples are the nonmonotonic behavior of the electrostatic potential and attractive interactions between equally charged surfaces. These predictions are certainly remarkable and, on paper, they can have an effect on experimentally measurable quantities (for instance, electrophoretic mobility). Even so, these new approaches have scarcely been applied in practice. Thus a critical survey on the relevance of ion size correlation in real systems is also included. Overcharging of macroions can also be brought about by adsorption of oppositely charged polyelectrolytes. Noteworthy examples and theoretical approaches for them are also briefly reviewed.

It is known that phosphatidylserine (PS(-)) lipids have a very similar affinity for Ca(2+) and Mg(2+) cations, as revealed by electrokinetic and stability experiments. However, despite this similar affinity, experimental evidence shows that the presence of Ca(2+) or Mg(2+) induces very different aggregation behavior for PS(-) liposomes as characterized by their fractal dimensions. Also, turbidity measurements confirm substantial differences in aggregation behavior depending on the presence of Ca(2+) or Mg(2+) cations. These puzzling results suggest that although these two cations have a similar affinity for PS(-) lipids, they induce substantial structural differences in lipid bilayers containing each of these cations. In other words, these cations have strong ion-specific effects on the structure of PS(-) membranes. This interpretation is supported by all-atomic molecular-dynamics simulations showing that Ca(2+) and Mg(2+) cations have different binding sites and induce different membrane hydration. We show that although both ions are incorporated deep into the hydrophilic region of the membrane, they have different positions and configurations at the membrane. Absorbed Ca(2+) cations present a peak at a distance ~2 nm from the center of the lipid bilayer, and their most probable binding configuration involves two oxygen atoms from each of the charged moieties of the PS molecule (phosphate and carboxyl groups). In contrast, the distribution of absorbed Mg(2+) cations has two different peaks, located a few angstroms before and after the Ca(2+) peak. The most probable configurations (corresponding to these two peaks) involve binding to two oxygen atoms from carboxyl groups (the most superficial binding peak) or two oxygen atoms from phosphate groups (the most internal peak). Moreover, simulations also show differences in the hydration structure of the membrane: we obtained a hydration of 7.5 and 9 water molecules per lipid in simulations with Ca(2+) and Mg(2+), respectively.

The compaction of DNA by cationic liposomes constituted by a mixture of a cationic lipid, dioctadecyldimethylammonium bromide (DODAB), and a zwitterionic lipid, 1,2-dioleoyl-sn-glycero-3-phosphatidylethanolamine (DOPE) or 1,2-dilauroyl-sn-glycero-3-phosphocholine (DLPC), has been evaluated by means of experimental studies (electrophoretic mobility, conductometry, cryogenic electron transmission microscopy or cryo-TEM, and fluorescence spectroscopy) as well as theoretical calculations. This information reveals that DODAB/DOPE and DODAB/DLPC liposomes are mostly spherical and unilamellar, with a mean diameter of around 70 and 61 nm, respectively, a bilayer thickness of 4.5 nm, and gel-to-fluid transition temperatures, T(m), of around 19 and 28 degrees C, respectively. Their positively charged surfaces efficiently compact the negatively charged DNA by means of a strong entropically driven surface interaction that yields DODAB/DOPE-DNA and DODAB/DLPC-DNA lipoplexes as confirmed by zeta potential and ethidium bromide fluorescence intercalation assays. These experiments have permitted as well the evaluation of the different microenvironments of varying polarity of the DNA helix, liposomes, and/or lipoplexes. DODAB/DOPE-DNA and DODAB/DLPC-DNA lipoplexes have been characterized by isoneutrality ratios (L/D)(phi) of around 4.7 and 4.8, respectively, a more fluid membrane than that of the parent liposomes, and T(m) around 24 and 28 degrees C, respectively, as revealed by fluorescence anisotropy. Cryo-TEM micrographs reveal a rich scenario of nanostructures and morphologies, from unilamellar DNA-coated liposomes to multilamellar lipoplexes passing through cluster-like structures. Phase diagrams (aggregation and re-entrant condensation phenomena), calculated by means of a phenomenological theory, have confirmed the experimental concentration domains and the isoneutrality conditions. The influence of helper lipid in the compaction process, as well as the optimum choice among those herein chosen, has been analyzed.