Enhanced Uptake of Integral Membrane Proteins by Cubic Nanoparticles

Abstract

Self-assembled lipidic cubic phases are attracting increasing interest as biocompatible carriers of large biomolecules including proteins, peptides, DNA and drugs.1 Their unique structure of interpenetrating but unconnected water channels divided by a lipid bilayer can accommodate hydrophobic, hydrophilic and amphiphilic moieties without significant structural perturbation. This has led to their use in a diverse range of applications including the delivery of drugs and other active agents, as biomimetic crystallization media for membrane proteins, as the basis of biofuel cells, and as biosensors.2Lipidic cubic phases can be emulsified into diluted non-viscous aqueous dispersions consisting of cubic nanoparticles, offering significant advantages for many of the applications listed above.3 Here we have incorporated an integral membrane protein and important neurological drug target within cubic nanoparticles. We have characterised the structural effect on the micro- and meso-scale properties of the nanoparticles. In addition we have shown that protein loading can be significantly enhanced by doping the cubic nanoparticles with a second amphiphile which chemically binds to the integral membrane protein.1Yaghmur A, Glatter O. Advances in Colloid and Interface Science 2009; 147-148; 333-342.2Nazaruk E, Bilewicz R, Lindblom G, Lindholm-Sethson B. Anal Bioanal Chem 2008; 391; 1569-1578.3Spicer PT. Current Opinion in Colloid & Interface Science 2005; 10; 274 - 279.