A solution NMR view of lipidic cubic phases: Structure, dynamics, and beyond

Nuclear magnetic resonance (NMR) spectroscopy is well -established nowadays for the elucidation of the 3D structures of proteins and protein complexes, the evaluation of biomolecular dynamics with atomistic resolution across a range of time scales, the screening of drug candidates with site specificity, and for the quantitation of molecular translational diffusion. Lyotropic lipidic cubic phases (LCPs) are lipid bilayer-based materials with a complex geometry, formed via the spontaneous self -assembly of certain lipids in an aqueous environment at specific temperature ranges. LCPs have been successfully applied to the in meso crystallization of membrane proteins for structural studies by X-ray crystallography, and have also shown promising potential for serving as matrices for drug and nutrient delivery/release in vivo . The characterization of the structural and dynamics properties of LCPs is of significant interest for the application of these materials. Here we present a systematic review detailing the characterization of LCPs by solution NMR. Using LCPs formed by monoolein (MO) as an example, various aspects of LCPs readily accessible by solution NMR are covered, including spectral perturbation in the presence of additives, quantification of hydration levels, 13 C relaxation -based measurements for studying atom -specific dynamics along the MO hydrocarbon chain, PGSE NMR measurement of translational diffusion and its correlation with release profiles, and the encapsulation of soluble proteins in LCPs. A brief discussion of future perspectives for the characterization of LCPs by solution NMR is also presented.