Complexes between membrane proteins (MPs) and amphipols (APols) can be obtained (i) by transferring to APols a detergent-solubilized MP, (ii) by directly extracting a membrane-bound one, (iii) by folding in APols a denatured MP, or (iv) by synthesizing it in vitro in the presence of APol. The complexes comprise a belt of APol that surrounds the transmembrane region of the protein and, if available, protein-bound lipids. Trapping with APols very generally maintains the activity of the protein, but a few cases of reversible inhibition have been observed. Most APol-trapped MPs are more stable, and generally much more so, than their detergent-solubilized counterparts. Three mechanisms appear to contribute to this stabilization: (i) reduction of the hydrophobic sink, (ii) the intrinsically less dissociating character of APols as compared to detergents, and (iii) damping by APols of MP dynamics, which raises the free energy barrier to unfolding. The latter phenomenon appears to be involved in the inhibition observed with some MPs, inasmuch as it can slow down conformational transitions. MPs trapped with APols can be transferred directly to detergent solutions, to other APols, to lipid vesicles, to lipidic mesophases, to black lipid films, or to cell membranes, as well as, indirectly, to nanodiscs or SMALPs.
