lipids, with most MPs widely separated one from another (Fig. 1.14A). This is very far from the actual
situation in real membranes, where MPs are crowded and, for many of them, interact one with another.
Molecular crowding is partially taken into account into the cartoon of Fig. 1.14B, but even there it is
underestimated. In fact, one can estimate, as more closely represented in the two cartoons of Fig. 1.15,
that in most membranes, only about four layers of lipids typically separate one MP from its neighbors
(Table 1.2), of which only two are “free,” in the sense that they are not in direct contact with a protein.
As we will see, lipids are found integrated in various ways into TM protein regions, and they may form
the “glue” that keep together MP supercomplexes (below, and Chap. 12).
1.5.2
Bound Lipids
The “open sea” concept carried by the original fluid mosaic model has influenced, more or less
consciously, the way biochemists and biophysicists have thought about lipids. Those have often
been considered as a mere two-dimensional solvent, whose bulk physical properties, such as thickness,
fluidity, deformability, charge distribution, internal variations of dielectric constant or local pressure,
and so on, were felt to be important for the folding, assembly, stability, and function of MPs (for
discussions, see e.g. Cevc and Marsh 1987; Lee 2004, 2011a, b; Andersen and Koeppe 2007; Marsh
2008; Phillips et al. 2009; Lundbaek et al. 2010; Anishkin et al. 2014, and references therein). These
factors are undoubtedly important in the membrane-bound state of some MPs, as exemplified by their
role in controlling, for instance, the opening and closing of mechanosensitive channels (see e.g. Battle
et al. 2015; Teng et al. 2015, and references therein). However, their importance should not be
overestimated. That the loss of membrane-induced physical constraints plays a role in the instability
and/or dysfunction of detergent-solubilized MPs is more often invoked than documented (cf. Chap. 2).
Whether this loss matters or not, and to which extent, is certainly protein dependent, given that many
MPs are functional in their absence (Chaps. 2 and 5) and that a surprisingly high number of them can
fold from a denatured to a functional state in non-bilayer environments (reviewed in Popot 2014; see
Chap. 6).
Fig. 1.15 Two views of the crowding of membrane proteins in (A) the inner and outer membranes of an
E. coli cell (from Goodsell 1991, # 2011 Elsevier Ltd. All rights reserved) and (B) a generic membrane
(From Engelman 2005, # 2005 Macmillan Publishers Limited, Nature. All rights reserved).
1.5 Membrane Protein/Lipid Interactions
25
situation in real membranes, where MPs are crowded and, for many of them, interact one with another.
Molecular crowding is partially taken into account into the cartoon of Fig. 1.14B, but even there it is
underestimated. In fact, one can estimate, as more closely represented in the two cartoons of Fig. 1.15,
that in most membranes, only about four layers of lipids typically separate one MP from its neighbors
(Table 1.2), of which only two are “free,” in the sense that they are not in direct contact with a protein.
As we will see, lipids are found integrated in various ways into TM protein regions, and they may form
the “glue” that keep together MP supercomplexes (below, and Chap. 12).
1.5.2
Bound Lipids
The “open sea” concept carried by the original fluid mosaic model has influenced, more or less
consciously, the way biochemists and biophysicists have thought about lipids. Those have often
been considered as a mere two-dimensional solvent, whose bulk physical properties, such as thickness,
fluidity, deformability, charge distribution, internal variations of dielectric constant or local pressure,
and so on, were felt to be important for the folding, assembly, stability, and function of MPs (for
discussions, see e.g. Cevc and Marsh 1987; Lee 2004, 2011a, b; Andersen and Koeppe 2007; Marsh
2008; Phillips et al. 2009; Lundbaek et al. 2010; Anishkin et al. 2014, and references therein). These
factors are undoubtedly important in the membrane-bound state of some MPs, as exemplified by their
role in controlling, for instance, the opening and closing of mechanosensitive channels (see e.g. Battle
et al. 2015; Teng et al. 2015, and references therein). However, their importance should not be
overestimated. That the loss of membrane-induced physical constraints plays a role in the instability
and/or dysfunction of detergent-solubilized MPs is more often invoked than documented (cf. Chap. 2).
Whether this loss matters or not, and to which extent, is certainly protein dependent, given that many
MPs are functional in their absence (Chaps. 2 and 5) and that a surprisingly high number of them can
fold from a denatured to a functional state in non-bilayer environments (reviewed in Popot 2014; see
Chap. 6).
Fig. 1.15 Two views of the crowding of membrane proteins in (A) the inner and outer membranes of an
E. coli cell (from Goodsell 1991, # 2011 Elsevier Ltd. All rights reserved) and (B) a generic membrane
(From Engelman 2005, # 2005 Macmillan Publishers Limited, Nature. All rights reserved).
1.5 Membrane Protein/Lipid Interactions
25