Making membrane proteins water-soluble by trapping them with amphipathic polymers rather than detergents.
In a solution of detergent-solubilized membrane protein (MP), detergent molecules are in a constant equilibrium between monomers, micelles, and the surfactant layer that covers the transmembrane region of the protein and makes it hydrophilic. To prevent MPs from aggregating, they must be handled above the CMC of the detergent, i.e. in the presence of free micelles, which is a major cause of inactivation.
The original idea behind the concept of amphipols was to devise molecules that would have such a high affinity for the surface of the protein that they would never dissociate, or, at least, that their equilibrium distribution would be so strongly displaced in favor of the surface that traces of free surfactant in the solution would suffice to keep the protein soluble. As a result, the micellar phase, which, in detergent solutions, acts as a hydrophobic sink that dissolves bound lipids, cofactors, and subunits, thereby destabilizing MPs, would essentially vanish.
Such a desirable result can a priori be achieved by resorting to surfactants that would carry not one or a few, but a large number of hydrophobic chains. This led to the design of 'amphipols' (APols), namely short amphipathic polymers that are able to keep individual MPs water-soluble in their native state under the form of small hydrophilic complexes (for reviews, see refs. 1-6).
The structure and solution properties of APols and MP/APol complexes have been extensively studied, and many applications have been or are being explored: