Effects of Cations on the Behaviour of Lipid Cubic Phases

Abstract

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 () to the double diamond phase () 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 () to the inverse hexagonal phase (HII) is observed occurring at higher mole fractions of DOPE than in pure water.

Cubosomes: The Next Generation of Smart Lipid Nanoparticles?

“…The DOPE containing cubic phases were not similarly affected although the transition to the hexagonal phase was shifted to higher mole fractions of DOPE. [98] In cubosome systems, salts have been exploited as a method to influence vesicle to cubosome transitions and reversibly form cubosomes, [99] study calcium triggered phase transitions, [100,101] in ionic surfactants incorporated into cubosomes and to vary ionic strength to induce phase transitions. [102] Whilst there are clearly many questions still to be addressed in the rational design of cubosomes, there is significant information and characterisation that already exists to enable the field to begin engineering tailor-made cubosomes for diverse applications.…”

Interaction of Small Ionic Species With Phospholipid Membranes: The Role of Metal Coordination

“…Yet, in model membrane studies ions were found to affect membrane structure and stability. Ca 2+ and Mg 2+ were shown to promote membrane fusion and permeability (Papahadjopoulos et al, 1977;Newton, 1978;Duzgunes et al, 1981;Brasnett et al, 2017). Alkaline and alkaline earth cations can cause a shift in phase transition temperatures (Garidel and Blume, 1999) and cause transient poration at the phase transition temperature of anionic lipids (Garidel and Blume, 2005;Riske et al, 2009).…”

Optimized reconstitution of membrane proteins into synthetic membranes

“…The factors lipid/polymer-toprotein ratio (LPR or PPR, w/w), detergent concentration (OG) and pH value were determined to be critical for a functional reconstitution of PR-GFP 7,8 . The buffer composition and especially the salt concentration can have a strong impact on the vesicle formation and stability of the protein in solution, too high or too low concentrations would lead to agglomeration and lossof-protein during its reconstitution 34,35 . Here, 150 mM KCl is used throughout the experiments which was determined to be suitable for PR-GFP 17,29 .…”

“…We followed the design proposed by Jones and Nachtsheim called definitive screening design which allows a one-step screening and optimization process 34,35 . All experimental designs were created using the DoE module of the software JMP (SAS).…”