Controlling micellar structure for membrane protein crystallization

Current crystallization strategies for membrane proteins involve solubilization in surfactant solutions and consequent modification of solution properties through addition of precipitants. A fundamental understanding of the role of surfactants on the overall interactions among protein-surfactant complexes is crucial to produce well-ordered crystals, yet is still missing. As a result, membrane proteins are only a very small fraction of the structures deposited in the Protein Data Bank, with enormous disadvantages to the structural biology and drug design communities. We use phase behavior studies and small-angle neutron scattering experiments to characterize solution properties of short chain alkyl monoglucosides with additives commonly used to promote crystallization, specifically polyethylene glycol and more hydrophobic surfactants. By SANS measurements analyzed with the generalized indirect Fourier transformation we are able to quantify the range and the strength of micellar interactions in solutions near the liquid-liquid phase boundary. Results give a quantitative framework to understand the role of phase boundaries in tuning micellar interactions and explain how such features can affect protein-surfactant assemblies.