Detergents are routine tools in biomembranes research, being essential for identification and characterization of solubilized micellar proteins. Yet, solubilization of biomembranes has not been systematically studied because of the complex composition of biomembranes. Therefore, much work has been devoted to solubilization of the relatively simple model membranes known as liposomes. Much data is available on the self-assembly of mixtures of bilayer-forming amphiphiles, particularly phospholipids, and micelle-forming amphiphiles, commonly denoted detergents. Here we review on the thoroughly investigated structure of such mixed assemblies, the theoretically rationalized phase diagrams and their dependence on various factors and the mechanisms of the composition-induced phase transformations between micellar and lamellar structures. The structure of such mixed assemblies is rationalized in terms of the balance between the large spontaneous curvature of the “curvophilic” detergent and the “curvophobic” phospholipids. Specifically, we propose that solubilization is the result of a balance between two parameters: (i) the energy associated with bending of phospholipid monolayers into a curved micellar surface, and (ii) the energy associated with filling the void in the center of the resultant mixed micelle.
We show that reliable data on the phase boundaries, and their dependence on various conditions, are consistent with this hypothesis, even if the data might have been interpreted differently. To explain the mechanism involved in solubilization, we first discuss previous data and ideas regarding this process. An important previous finding is that membrane solubilization by some detergents is relatively slow and that the common attribute of these detergents is that their trans-bilayer movement, commonly denoted “flip flop” is very slow. In other words, only detergents that can “flip” into the inner monolayer cause relatively rapid solubilization. Another important process is that detergents induce size growth of small liposomes, including those formed during solubilization, as well as those formed upon reconstitution of liposomes from mixed micelles.
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