Molecular Self-assembly and Interactions in Solutions of Membrane Proteins and Surfactants

Understanding how surfactants bind to membrane proteins and affect their stability is essential for the manipulation of these proteins outside native membranes. Contrast variation studies by analytical ultracentrifugation and small-angle neutron scattering enable measurement of the composition of the protein-surfactant complexes and determination of the thickness of the surfactant shell bound to the protein. When bacteriorhodopsin is solubilized in solutions of alkyl polyglucosides, the surfactant layer around the protein has a thickness equal to a single amphiphile molecule or larger. The thickness of the surfactant shell increases with increasing surfactant length, and it is generally unrelated to the aggregation number of the micelles even for small and predominantly hydrophobic membrane proteins. Studies of bacteriorhodopsin activity by absorption spectroscopy show that the surfactant arrangement as a single layer directly correlates with a limited stability of the protein over time. A similar connection between surfactant binding and protein stability is observed when bacteriorhodopsin is illuminated and active in pumping protons. These results are useful to guide the choice of surfactant solutions for optimal solubilization of membrane proteins, which is the key to increasing success rates in crystallization and functional studies of these proteins.