Chemical Structure, Synthesis,
and Physical-Chemical Properties
of Amphipols
4
Summary
Many different chemical structures have been shown to yield amphipols (APols), that is
amphipathic polymers that are able to keep individual membrane proteins (MPs)
soluble in their native state under the form of small complexes. They have in common
to be polydisperse (a consequence of their mode of synthesis, but, a priori, not a
requirement), of moderate size (in general 20 kDa), and to feature either interspersed
or alternating hydrophilic and hydrophobic units or a succession of identical amphiphilic ones. The presence of a large number of hydrophilic moieties is essential to
ensuring the solubility of the many hydrophobic groups that will interact with the
transmembrane surface of MPs, and the properties of these moieties – such as pHor calcium-dependent solubility – affect those of APols and MP/APol complexes. In
aqueous solutions, most APols self-associate into small, micelle-like particles, of which
hydrophobic moieties occupy the core and hydrophilic ones the surface. Whereas
individual APol molecules are polydisperse, the particles they assemble into are nearly
monodisperse, reflecting the existence of a thermodynamically optimal size. Because
APols are relatively large molecules, grafting them with functional groups is generally
possible without affecting their solution properties, which has permitted the development of a vast variety of labeled or tagged APols.
4.1
Introduction
In the preceding chapter, we have examined a number of surfactants or surfactant mixtures that provide
ways to handle membrane proteins (MPs) in detergent-free aqueous solutions (nanodiscs, amphipathic
peptides, fluorinated surfactants, etc.) or while limiting their exposure to detergents (bicelles).
Amphipols (APols) represent a further alternative. APols are usefully defined as “amphipathic
polymers that are able to keep individual MPs soluble in their native form under the form of small
complexes” (Popot 2010; Popot et al. 2011). Strictly speaking, such a definition could be applied to
nanodiscs (NDs), peptitergents, or lipopeptides, given that proteins and peptides are polymers.
However, the chemical structure of polypeptide chains endows them with the ability to adopt welldefined secondary structures, and for all three systems mentioned above, it is the resulting folded
# 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_4
151
and Physical-Chemical Properties
of Amphipols
4
Summary
Many different chemical structures have been shown to yield amphipols (APols), that is
amphipathic polymers that are able to keep individual membrane proteins (MPs)
soluble in their native state under the form of small complexes. They have in common
to be polydisperse (a consequence of their mode of synthesis, but, a priori, not a
requirement), of moderate size (in general 20 kDa), and to feature either interspersed
or alternating hydrophilic and hydrophobic units or a succession of identical amphiphilic ones. The presence of a large number of hydrophilic moieties is essential to
ensuring the solubility of the many hydrophobic groups that will interact with the
transmembrane surface of MPs, and the properties of these moieties – such as pHor calcium-dependent solubility – affect those of APols and MP/APol complexes. In
aqueous solutions, most APols self-associate into small, micelle-like particles, of which
hydrophobic moieties occupy the core and hydrophilic ones the surface. Whereas
individual APol molecules are polydisperse, the particles they assemble into are nearly
monodisperse, reflecting the existence of a thermodynamically optimal size. Because
APols are relatively large molecules, grafting them with functional groups is generally
possible without affecting their solution properties, which has permitted the development of a vast variety of labeled or tagged APols.
4.1
Introduction
In the preceding chapter, we have examined a number of surfactants or surfactant mixtures that provide
ways to handle membrane proteins (MPs) in detergent-free aqueous solutions (nanodiscs, amphipathic
peptides, fluorinated surfactants, etc.) or while limiting their exposure to detergents (bicelles).
Amphipols (APols) represent a further alternative. APols are usefully defined as “amphipathic
polymers that are able to keep individual MPs soluble in their native form under the form of small
complexes” (Popot 2010; Popot et al. 2011). Strictly speaking, such a definition could be applied to
nanodiscs (NDs), peptitergents, or lipopeptides, given that proteins and peptides are polymers.
However, the chemical structure of polypeptide chains endows them with the ability to adopt welldefined secondary structures, and for all three systems mentioned above, it is the resulting folded
# 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_4
151