freshwater, or the fluids stored inside our organisms. The inside of each cell, and each compartment
within a cell, is also watery, and cells and multicellular organisms that must survive in dry
environments, like spores, seeds, or tardigrades, go to extreme lengths to limit and survive partial
desiccation. The fluid inside a cell, the cytoplasm, is a concentrated soup of molecules and ions, those
imported by the cell, such as inorganic ions or nutrients, and those manufactured by it, be they small –
sugars, for instance – or very large, such as the nucleic acids into the sequence of which is stored and
thanks to which is exploited the genetic information, as well as the proteins that catalyze most
biological reactions. The three-dimensional (3D) structure adopted by these macromolecules depends
in large part on their interactions with water: for most water-soluble proteins, for instance, the main
driving force that will initiate the positioning in space of their hundreds or thousands of amino-acid
residues is the segregation of hydrophilic side chains, which oppose being deprived of water, from
hydrophobic ones, which tend to segregate away from it. The force underlying this behavior is the
strong interactions water molecules establish with one another. Unless those are replaced by even
stronger ones, such as those that water molecules can establish with ions or strongly polar groups,
foreign molecules or groups will be repelled and expelled from the water phase, an effect known as the
hydrophobic effect (see e.g. Tanford 1980; Israelachvili 2011, and references therein). The hydrophobic effect is a powerful organizing phenomenon on which much of life as we know it is based.
The compartmentalization of living matter relies on the behavior of special classes of amphipathic molecules, that is in the case of living matter, molecules that comprise groups that interact
favorably with water (called hydrophilic) and groups that are repelled by it (called hydrophobic). One
can imagine, design, and put to work other types of amphipathic molecules, for instance, molecules
that comprise groups that are soluble in hydrocarbons and groups that are soluble in fluorocarbons, all
of them being highly insoluble in water (see Chap. 3, § 3.5). As used in this book, the term
amphipathic, however, will always refer to molecules that comprise chemical groups with differential
affinity for water. We have already noted that proteins are amphipathic, being comprised of both
hydrophilic and hydrophobic groups, and that this combination is a major factor driving their 3D
folding. As typical examples of smaller amphipathic biological molecules, Fig. 1.1 shows the structure
of a selection of polar lipids. Each of these compounds comprises one or more polar group(s) and one
or more apolar one(s), which generally are segregated at opposite ends of an elongated molecule. The
polar end can carry charged moieties, e.g. phosphate, carboxylates or ammonium groups, or nonionic
but hydrogen-bonding groups, such as hydroxyles. When exposed to water, these groups will tend to
associate with it, because the polar interactions they establish with it overcome those of water
molecules with themselves. The other end of most polar lipids is generally comprised of one, two
(in most cases), or more hydrocarbon chains, either saturated or unsaturated, in which the partial
charges carried by the hydrogen and carbon atoms are very small. Such groups are not polar enough to
compete with the strong interactions that water molecules establish one with another, and they are
repelled by it.
When a single molecule of lipid is let loose in a droplet of water, it will equilibrate between the
bulk and, if available, the air/water interface. At the interface, the polar head group can stay in contact
with water, whereas the hydrophobic acyl chains can be expulsed from it. Because less water
molecules are perturbed, this state is at a lower standard chemical potential (μ
) than is an isolated
lipid molecule fully surrounded with water. An equilibrium establishes itself between entropy, which
tends to dilute the molecules in the bulk, and the hydrophobic effect, which tends to push them to the
surface. Water molecules are themselves at a higher standard chemical potential at the interface than
they are in the bulk, because they cannot satisfy as efficiently the hydrogen bonds they form with their
neighbors. Creating a certain area of air/water interface therefore costs energy, which is at the origin of
the surface tension that tends to diminish the area of the interface: this is why a droplet of water
deposited on a hydrophobic surface such as that of Teflon takes up a nearly spherical form.
2
1 Membrane Proteins and Their Natural Environment
within a cell, is also watery, and cells and multicellular organisms that must survive in dry
environments, like spores, seeds, or tardigrades, go to extreme lengths to limit and survive partial
desiccation. The fluid inside a cell, the cytoplasm, is a concentrated soup of molecules and ions, those
imported by the cell, such as inorganic ions or nutrients, and those manufactured by it, be they small –
sugars, for instance – or very large, such as the nucleic acids into the sequence of which is stored and
thanks to which is exploited the genetic information, as well as the proteins that catalyze most
biological reactions. The three-dimensional (3D) structure adopted by these macromolecules depends
in large part on their interactions with water: for most water-soluble proteins, for instance, the main
driving force that will initiate the positioning in space of their hundreds or thousands of amino-acid
residues is the segregation of hydrophilic side chains, which oppose being deprived of water, from
hydrophobic ones, which tend to segregate away from it. The force underlying this behavior is the
strong interactions water molecules establish with one another. Unless those are replaced by even
stronger ones, such as those that water molecules can establish with ions or strongly polar groups,
foreign molecules or groups will be repelled and expelled from the water phase, an effect known as the
hydrophobic effect (see e.g. Tanford 1980; Israelachvili 2011, and references therein). The hydrophobic effect is a powerful organizing phenomenon on which much of life as we know it is based.
The compartmentalization of living matter relies on the behavior of special classes of amphipathic molecules, that is in the case of living matter, molecules that comprise groups that interact
favorably with water (called hydrophilic) and groups that are repelled by it (called hydrophobic). One
can imagine, design, and put to work other types of amphipathic molecules, for instance, molecules
that comprise groups that are soluble in hydrocarbons and groups that are soluble in fluorocarbons, all
of them being highly insoluble in water (see Chap. 3, § 3.5). As used in this book, the term
amphipathic, however, will always refer to molecules that comprise chemical groups with differential
affinity for water. We have already noted that proteins are amphipathic, being comprised of both
hydrophilic and hydrophobic groups, and that this combination is a major factor driving their 3D
folding. As typical examples of smaller amphipathic biological molecules, Fig. 1.1 shows the structure
of a selection of polar lipids. Each of these compounds comprises one or more polar group(s) and one
or more apolar one(s), which generally are segregated at opposite ends of an elongated molecule. The
polar end can carry charged moieties, e.g. phosphate, carboxylates or ammonium groups, or nonionic
but hydrogen-bonding groups, such as hydroxyles. When exposed to water, these groups will tend to
associate with it, because the polar interactions they establish with it overcome those of water
molecules with themselves. The other end of most polar lipids is generally comprised of one, two
(in most cases), or more hydrocarbon chains, either saturated or unsaturated, in which the partial
charges carried by the hydrogen and carbon atoms are very small. Such groups are not polar enough to
compete with the strong interactions that water molecules establish one with another, and they are
repelled by it.
When a single molecule of lipid is let loose in a droplet of water, it will equilibrate between the
bulk and, if available, the air/water interface. At the interface, the polar head group can stay in contact
with water, whereas the hydrophobic acyl chains can be expulsed from it. Because less water
molecules are perturbed, this state is at a lower standard chemical potential (μ
) than is an isolated
lipid molecule fully surrounded with water. An equilibrium establishes itself between entropy, which
tends to dilute the molecules in the bulk, and the hydrophobic effect, which tends to push them to the
surface. Water molecules are themselves at a higher standard chemical potential at the interface than
they are in the bulk, because they cannot satisfy as efficiently the hydrogen bonds they form with their
neighbors. Creating a certain area of air/water interface therefore costs energy, which is at the origin of
the surface tension that tends to diminish the area of the interface: this is why a droplet of water
deposited on a hydrophobic surface such as that of Teflon takes up a nearly spherical form.
2
1 Membrane Proteins and Their Natural Environment