Applications of the lipidic cubic phase: From controlled release and uptake to in meso crystallization of membrane proteins

The lipidic cubic phase consists of a pair of interpenetrating but non-contacting aqueous channels separated by a single, highly curved continuous lipid bilayer. Because of its unique microstructure and dual nature (hydrophobic/hydrophilic character), the cubic phase finds use in controlled release and uptake. With a view to exploiting these features in combination with small molecule and proteinaceous drugs, a systematic approach aimed at understanding how the transport properties of the cubic phases are controlled by phase identity and microstructure (aqueous channel size) and by the physical and chemical properties of the drug itself (molecular size, shape) was taken. Furthermore, tailored release was demonstrated by adjusting electrostatic interaction strength and by His-tag displacement. Additional control was demonstrated by alkylating a water-soluble additive in such a manner that it interacted with the lipid bilayer. The results show that by varying the alkyl chain length, the release from the cubic phase can be controlled/prolonged in a systematic manner. While the previous study examined diffusion within the water channels, the study was extended to include lipid-soluble additives. For this purpose, the diffusion of three hydrophobic additives ranging in size from a small molecule (354 g/mol) to a huge multisubunit membrane protein (∼129 kDa) in the lipid bilayer was quantified. This made use of commercial quartz tubing (microcuvettes), which allowed for the measurement of small sample volumes (1--5 muL). The results compare well with those obtained using more complicated techniques. Finally, the possibility of exploiting the "sponge-like" properties of the cubic phase in wastewater remediation was investigated. For this purpose, Myverol 18--99K, a relatively inexpensive commercial and biocompatible material, was used as the source lipid. Accordingly, the uptake of phenol, a wastewater contaminant of note, into pre-formed cubic phase prepared from Myverol has been quantified. This was compared to uptake by "neat" or pure Myverol, by a colloidal dispersion of the Myverol-based cubic phase referred to as cubosomes and by activated carbon.