It may seem strange that MP/detergent complexes do not immediately dissociate once exposed to
vacuum, a medium in which the hydrophobic effect is absent and where there is, therefore, little free
energy gain to be expected from adsorbing the detergent’s alkyl tails onto the TM surface of the
protein, whereas entropy favors dissociation (note however that Van der Waals forces do persist and, at
variance with what would occur in a hydrocarbon solvent, can make significant contributions; see Liu
et al. 2009). In a low dielectric environment and in the absence of competition with water, polar
interactions between detergent polar heads are reinforced. It is certainly significant that, during an
ESI-MS experiment, Triton X-100 is stripped from MPs at much lower energies than dodecylmaltoside
(DDM) (Konijnenberg et al. 2014) (cf. legend to Fig. 14.2): the polar moieties of Triton, which consist
of polyethylene glycol, cannot establish hydrogen bonds between themselves, whereas the maltosyl
headgroups of DDM can. A similar effect is seen when comparing C 8 E 4 and octylglucoside (Reading
et al. 2015). Molecular dynamics (MD) studies (Rouse et al. 2013) do show that, upon simulated
transfer of a MP/DDM complex from water to vacuum (and at variance with what is observed with
ionic detergents), very little reorganization of the complex is observed (Fig. 14.5A, B). In the course of
the simulation, most (but not all) water molecules evaporate (Fig. 14.5C, D), and most of the hydrogen
bonds that the detergent formed with water disappear (Fig. 14.5E), to be replaced by DDM-DDM ones
(Fig. 14.5F).
MS studies of MP/APol complexes are only at their beginning, but they already point to several
interesting applications. Published studies are compiled in Table 14.1 (for earlier overviews, see Popot
et al. 2011; Zoonens and Popot 2014). They fall into three categories:
(i) MALDI-TOF studies of the mass of MPs and associated cofactors, such as lipids and hemes
(Studies 14.1 and 14.2);
(ii) ESI and ESI-IM studies of MPs and MP complexes, aiming, in particular, to examine
whether using APols for stabilizing fragile MPs in aqueous solutions (Chap. 5, § 5.6) is
compatible with MS studies (Studies 14.3 and 14.4, and 14.6–14.8);
(iii) Proteomic studies, where APols are exploited to simplify the production and recovery of
MPs and proteolytic peptides (Studies 14.5 and 14.9).
Amphipols and mass spectrometry of membrane proteins
(# 2018 by Francis Haraux).
630
14 The Use of Amphipols in Mass Spectrometry
vacuum, a medium in which the hydrophobic effect is absent and where there is, therefore, little free
energy gain to be expected from adsorbing the detergent’s alkyl tails onto the TM surface of the
protein, whereas entropy favors dissociation (note however that Van der Waals forces do persist and, at
variance with what would occur in a hydrocarbon solvent, can make significant contributions; see Liu
et al. 2009). In a low dielectric environment and in the absence of competition with water, polar
interactions between detergent polar heads are reinforced. It is certainly significant that, during an
ESI-MS experiment, Triton X-100 is stripped from MPs at much lower energies than dodecylmaltoside
(DDM) (Konijnenberg et al. 2014) (cf. legend to Fig. 14.2): the polar moieties of Triton, which consist
of polyethylene glycol, cannot establish hydrogen bonds between themselves, whereas the maltosyl
headgroups of DDM can. A similar effect is seen when comparing C 8 E 4 and octylglucoside (Reading
et al. 2015). Molecular dynamics (MD) studies (Rouse et al. 2013) do show that, upon simulated
transfer of a MP/DDM complex from water to vacuum (and at variance with what is observed with
ionic detergents), very little reorganization of the complex is observed (Fig. 14.5A, B). In the course of
the simulation, most (but not all) water molecules evaporate (Fig. 14.5C, D), and most of the hydrogen
bonds that the detergent formed with water disappear (Fig. 14.5E), to be replaced by DDM-DDM ones
(Fig. 14.5F).
MS studies of MP/APol complexes are only at their beginning, but they already point to several
interesting applications. Published studies are compiled in Table 14.1 (for earlier overviews, see Popot
et al. 2011; Zoonens and Popot 2014). They fall into three categories:
(i) MALDI-TOF studies of the mass of MPs and associated cofactors, such as lipids and hemes
(Studies 14.1 and 14.2);
(ii) ESI and ESI-IM studies of MPs and MP complexes, aiming, in particular, to examine
whether using APols for stabilizing fragile MPs in aqueous solutions (Chap. 5, § 5.6) is
compatible with MS studies (Studies 14.3 and 14.4, and 14.6–14.8);
(iii) Proteomic studies, where APols are exploited to simplify the production and recovery of
MPs and proteolytic peptides (Studies 14.5 and 14.9).
Amphipols and mass spectrometry of membrane proteins
(# 2018 by Francis Haraux).
630
14 The Use of Amphipols in Mass Spectrometry