(for reviews, see e.g. Neugebauer 1990; Sadaf et al. 2015). At variance with bilayer-forming lipids,
the polar head of detergents, taking into account its dynamics, electrostatic repulsion, etc., is more
bulky than their hydrophobic moiety. Upon assembling side-by-side, detergent molecules therefore
generate a convex rather than a flat interface with the aqueous solution. As a result, instead of forming
extended sheets like membrane lipids do, they aggregate into closed objects called micelles (see
Fig. 2.3). Depending on the relative size of the hydrophobic and hydrophilic moieties and other
molecular properties, micelles can be spherical, oblate (lenticular), prolate (cigar-like), or cylindrical
(see Table 1.1, lines 1 and 2, in Chap. 1). The surface of micelles is hydrophilic, their core hydrophobic. They provide the medium into which hydrophobic or amphipathic molecules, such as lipids, can
dissolve and become water-soluble.
As illustrated in Fig. 2.1, the polar head of detergents can be ionic and carry a net electric charge,
zwitterionic and globally neutral, or uncharged. In the latter case, water solubility results from the
presence of hydrogen-bonding groups, such as the ether groups of polyoxyethylene-based detergents
(Tritons, Tweens, C m E n , etc.) or hydroxyl groups, which are often carried by sugar moieties:
octylglucoside (OG) and dodecylmaltoside (DDM) are among the most widely used detergents in
membrane biochemistry.
Some detergents have more complex structures. DiC 6 - and diC 7 PC (both of them, confusingly,
customarily abbreviated DHPC in the literature) have the structure of a phospholipid, with two acyl
chains attached to a glycerophosphocholine head group. However, the chains are so short that DHPC
molecules behave as detergents, often used in solution NMR investigations of MPs, as well as in
bicelle-forming mixtures (for a discussion, see Hauser 2000; see § 2.3.1 and Chap. 3, § 3.2).
Some natural detergents (bile salts such as cholate and deoxycholate and their conjugated
derivatives – taurocholate, glycocholate, etc. – digitonin), or partially synthetic ones (CHAPS,
CHAPSO), are derived from a steroid, hydrophobic, polycyclic nucleus carrying (i) a polar head and
(ii) hydroxyl groups. The latter groups are concentrated on one face of the nucleus, making it laterally
amphipathic (Fig. 2.1). As will be described below (§ 2.2.2), this confers to the mixtures of these
detergents with lipids in aqueous solutions a very peculiar behavior as compared with less complex
detergents. Some modern semisynthetic detergents (“facial detergents”) have further built upon this
kind of structure (§ 2.5.1).
2.2.2
Physical-Chemical Properties
Because of their great theoretical interest as models of self-organizing systems and their extreme
practical importance, the physical-chemical properties of aqueous solutions of detergents have been
extensively studied (for reviews, see e.g. Tanford 1972, 1980; Israelachvili 2011). In the present
section, we will focus on those aspects that are particularly relevant to understanding issues to be
discussed in the next chapters.
The aggregation behavior exhibited by detergents in aqueous solutions is schematized in
Fig. 2.2. It results from the balance between entropy, which tends to disperse the molecules, and the
hydrophobic effect, which tends to bring their hydrophobic tails together (for a very clear introduction
to the thermodynamics of micelle formation, see Chap. 7 in Tanford 1980). The distribution of
detergent molecules between free monomers and molecules associated into micelles obeys a classic
monomer/oligomer equilibrium. However, because micelles usually comprise several tens of
molecules (typically 50–100, but for micelles of pure bile salts and their derivatives, which comprise
only a few), their formation resembles a phase transition: below a given concentration called the
critical micellar concentration (CMC), entropy dominates and micelles are essentially nonexistent.
Above the CMC, the concentration of monomers increases only very slowly, almost all new molecules
added to the solution associating into micelles. As a result, the concentration of micellar detergent in
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2 Extracting Membrane Proteins from Their Native Environment
the polar head of detergents, taking into account its dynamics, electrostatic repulsion, etc., is more
bulky than their hydrophobic moiety. Upon assembling side-by-side, detergent molecules therefore
generate a convex rather than a flat interface with the aqueous solution. As a result, instead of forming
extended sheets like membrane lipids do, they aggregate into closed objects called micelles (see
Fig. 2.3). Depending on the relative size of the hydrophobic and hydrophilic moieties and other
molecular properties, micelles can be spherical, oblate (lenticular), prolate (cigar-like), or cylindrical
(see Table 1.1, lines 1 and 2, in Chap. 1). The surface of micelles is hydrophilic, their core hydrophobic. They provide the medium into which hydrophobic or amphipathic molecules, such as lipids, can
dissolve and become water-soluble.
As illustrated in Fig. 2.1, the polar head of detergents can be ionic and carry a net electric charge,
zwitterionic and globally neutral, or uncharged. In the latter case, water solubility results from the
presence of hydrogen-bonding groups, such as the ether groups of polyoxyethylene-based detergents
(Tritons, Tweens, C m E n , etc.) or hydroxyl groups, which are often carried by sugar moieties:
octylglucoside (OG) and dodecylmaltoside (DDM) are among the most widely used detergents in
membrane biochemistry.
Some detergents have more complex structures. DiC 6 - and diC 7 PC (both of them, confusingly,
customarily abbreviated DHPC in the literature) have the structure of a phospholipid, with two acyl
chains attached to a glycerophosphocholine head group. However, the chains are so short that DHPC
molecules behave as detergents, often used in solution NMR investigations of MPs, as well as in
bicelle-forming mixtures (for a discussion, see Hauser 2000; see § 2.3.1 and Chap. 3, § 3.2).
Some natural detergents (bile salts such as cholate and deoxycholate and their conjugated
derivatives – taurocholate, glycocholate, etc. – digitonin), or partially synthetic ones (CHAPS,
CHAPSO), are derived from a steroid, hydrophobic, polycyclic nucleus carrying (i) a polar head and
(ii) hydroxyl groups. The latter groups are concentrated on one face of the nucleus, making it laterally
amphipathic (Fig. 2.1). As will be described below (§ 2.2.2), this confers to the mixtures of these
detergents with lipids in aqueous solutions a very peculiar behavior as compared with less complex
detergents. Some modern semisynthetic detergents (“facial detergents”) have further built upon this
kind of structure (§ 2.5.1).
2.2.2
Physical-Chemical Properties
Because of their great theoretical interest as models of self-organizing systems and their extreme
practical importance, the physical-chemical properties of aqueous solutions of detergents have been
extensively studied (for reviews, see e.g. Tanford 1972, 1980; Israelachvili 2011). In the present
section, we will focus on those aspects that are particularly relevant to understanding issues to be
discussed in the next chapters.
The aggregation behavior exhibited by detergents in aqueous solutions is schematized in
Fig. 2.2. It results from the balance between entropy, which tends to disperse the molecules, and the
hydrophobic effect, which tends to bring their hydrophobic tails together (for a very clear introduction
to the thermodynamics of micelle formation, see Chap. 7 in Tanford 1980). The distribution of
detergent molecules between free monomers and molecules associated into micelles obeys a classic
monomer/oligomer equilibrium. However, because micelles usually comprise several tens of
molecules (typically 50–100, but for micelles of pure bile salts and their derivatives, which comprise
only a few), their formation resembles a phase transition: below a given concentration called the
critical micellar concentration (CMC), entropy dominates and micelles are essentially nonexistent.
Above the CMC, the concentration of monomers increases only very slowly, almost all new molecules
added to the solution associating into micelles. As a result, the concentration of micellar detergent in
62
2 Extracting Membrane Proteins from Their Native Environment