Effects of glycerol and urea on micellization, membrane partitioning and solubilization by a non-ionic surfactant

We have studied the effect of two cosolvents, urea and glycerol, on the association and interactions of a surfactant, octaethyleneglycol dodecyl ether (C12EO8) and a phospholipid (POPC). We have measured the CMC, the partition coefficient, the effective mole fractions Xesat and Xesol at the onset and completion of the membrane-to-micelle transition (membrane solubilization), and the enthalpies of transfer of surfactant by ITC. Changes in membrane order and dynamics were characterized by time-resolved fluorescence anisotropy measurements of DPH, and micelle sizes and clouding by light scattering. The cosolvents have complex effects that are not governed by the well-known 'salting in' or 'salting out' effects on the solubility alone. Instead, urea and glycerol alter also the intrinsic curvature ('effective molecular shape') of the detergent and the order and packing of the membrane. These curvature effects have an unusual enthalpy/entropy balance and are not additive for lipid and detergent. The results shed light on the phenomena governing lipid-detergent systems in general and have a number of implications for the use of cosolvents in membrane protein studies.