Effects of Cations on the Behaviour of Lipid Cubic Phases

Inverse bicontinuous cubic structures formed by lipids have been demonstrated in a wide variety of applications, from a host matrix for proteins for crystallisation, to templates for nanoscale structures. Recent work has focused on tuning their properties to realize such applications, often by manipulating the structure by introducing other lipids with different properties such as charge or packing. However, they are often prepared in the presence of solutions containing salt, counteracting the effects, for example, charged lipids, and fundamentally changing the structures obtained. Here, we demonstrate the delicate interplay between electrostatic swelling in bicontinuous structures formed by monoolein (MO) doped with both negatively charged dioleyl phosphatidylglycerol (DOPG), and zwitterionic dioleyl phosphatidylethanolamine (DOPE), with the addition of mono-and divalent salts. The effect of adding salt to the charged phase changes the structure from the primitive cubic (Q(II)(P)) to the double diamond phase (Q(II)(D)) whilst still allowing for modest increases in lattice parameter of up to a nanometer. Contrasting this, the addition of salts to the non-charged phase, has minimal effect on the lattice parameter but now the transition from the (Q(II)(D)) to the inverse hexagonal phase (H-II) is observed occurring at higher mole fractions of DOPE than in pure water.