Alternatives to Detergents for Handling
Membrane Proteins in Aqueous Solutions 3
Summary
Attempts at substituting detergents with other surfactants for handling membrane
proteins (MPs) in aqueous solutions have a long history. They are based on three
main incentives: (i) trying to improve the stability of solubilized MPs; (ii) providing
them with an environment that, in its physical characteristics and/or its chemical
composition, is closer to the natural environment; and (iii) making them accessible
to technologies that are difficult or impossible to implement in the presence of
detergents. A first route is to reinsert the protein in a lipid bilayer, most often closed
upon itself in the form of lipid vesicles, sometimes forming a planar “black lipid
membrane.” This approach is obligatory when functional assays require the protein
to have access to two distinct aqueous compartments, but the objects formed are large,
if not macroscopic, and do not lend themselves well to most biophysical investigations.
A second route is to substitute totally or partially the detergent with other surfactants
while forming water-soluble particles of nanometric dimensions. The use of specially
developed amphipathic polymers called amphipols is one such approach, which will
be described in detail in Chaps. 4 and 5, but it is far from being the only one. In order
to provide a broader view of which systems are available to the experimenter, the
present chapter reviews the four principal alternatives to detergents and amphipols:
(i) bicelles, which are mixtures of lipids and detergents or short-chain lipids that,
under appropriate conditions, form disc-shaped bilayer fragments into which MPs
can integrate; (ii) nanodiscs, whose basic concept is similar to that of bicelles, but
in which the rim of the bilayer disc is stabilized by specially engineered proteins;
(iii) peptides or lipopeptides, which can either interact directly with the MP to be
solubilized or stabilize MP/lipid complexes; and (iv) fluorinated surfactants, which
resemble detergents in their chemical structure but whose hydrophobic chains contain
fluorine atoms, which make them lyophobic (poorly miscible with hydrocarbons); this
renders them less disruptive of the protein/protein and protein/lipid interactions that
stabilize MPs.
# Springer International Publishing AG, part of Springer Nature 2018
J. -L. Popot, Membrane Proteins in Aqueous Solutions, Biological and Medical Physics,
Biomedical Engineering, https://doi.org/10.1007/978-3-319-73148-3_3
97
Membrane Proteins in Aqueous Solutions 3
Summary
Attempts at substituting detergents with other surfactants for handling membrane
proteins (MPs) in aqueous solutions have a long history. They are based on three
main incentives: (i) trying to improve the stability of solubilized MPs; (ii) providing
them with an environment that, in its physical characteristics and/or its chemical
composition, is closer to the natural environment; and (iii) making them accessible
to technologies that are difficult or impossible to implement in the presence of
detergents. A first route is to reinsert the protein in a lipid bilayer, most often closed
upon itself in the form of lipid vesicles, sometimes forming a planar “black lipid
membrane.” This approach is obligatory when functional assays require the protein
to have access to two distinct aqueous compartments, but the objects formed are large,
if not macroscopic, and do not lend themselves well to most biophysical investigations.
A second route is to substitute totally or partially the detergent with other surfactants
while forming water-soluble particles of nanometric dimensions. The use of specially
developed amphipathic polymers called amphipols is one such approach, which will
be described in detail in Chaps. 4 and 5, but it is far from being the only one. In order
to provide a broader view of which systems are available to the experimenter, the
present chapter reviews the four principal alternatives to detergents and amphipols:
(i) bicelles, which are mixtures of lipids and detergents or short-chain lipids that,
under appropriate conditions, form disc-shaped bilayer fragments into which MPs
can integrate; (ii) nanodiscs, whose basic concept is similar to that of bicelles, but
in which the rim of the bilayer disc is stabilized by specially engineered proteins;
(iii) peptides or lipopeptides, which can either interact directly with the MP to be
solubilized or stabilize MP/lipid complexes; and (iv) fluorinated surfactants, which
resemble detergents in their chemical structure but whose hydrophobic chains contain
fluorine atoms, which make them lyophobic (poorly miscible with hydrocarbons); this
renders them less disruptive of the protein/protein and protein/lipid interactions that
stabilize MPs.
# Springer International Publishing AG, part of Springer Nature 2018
J. -L. Popot, Membrane Proteins in Aqueous Solutions, Biological and Medical Physics,
Biomedical Engineering, https://doi.org/10.1007/978-3-319-73148-3_3
97