Cellular Matters

Summary

The environment inside cells is weird and wonderful. The molecular storm blows like a hurricane in air thick as treacle, driving everything that happens. Large molecules, crowded together, fold into complex structures. Some of these then self-assemble to form nanoscale machines. These machines control a complex network of chemical reactions that transforms a chemical gradient into, ultimately, a new cell. The chapter ends with an overview of this network which structures the chapters to follow.

Take some finely powdered sugar and blow it through a flame. Actually, for safety’s sake, don’t. Instead, watch a video.¹ The result is a fireball as the sugar combines with oxygen in the air to form carbon dioxide and water. The equilibrium of the reaction is on the right, but it doesn’t happen at room temperature due to an energy barrier. The flame amplifies the molecular storm, raising the speed of oxygen molecules so they have enough kinetic energy to overcome the barrier. The energy is released into the environment as heat which ionises air to produce the fireball. The sugar gradient—a chemical disequilibrium—is dissipated as heat.

A living cell is driven by the same gradient. If we treat the cell as a black box, the source is a local concentration of glucose (or other sugars, or in general “food”), the sink is the environment into which the cell dissipates heat and matter. This is shown in the right panel of Fig. 9.1. So far, this is no more than a description of an engine. As with an engine, not all the glucose gradient is dissipated as heat, some is used to do work. At this level of abstraction, all we can say is that some of the work maintains the cell and some creates an approximate copy of the cell. While self-organising engines build themselves, living cells build copies of themselves. This is extraordinary in itself. In Chap. 14, we shall see that it is also extraordinary in thermodynamic terms.

Fig. 9.1

CellsFootnote

Source of photo: https://phil.cdc.gov/Details.aspx?pid=21924. Public domain.

Now let’s take a peek inside the black box. Letting the chemical energy in the sugar flow to the sink in one step would vaporise the cell. Instead, the cell splits the gradient into many smaller ones. Imagine a river flowing into a lake. It can do so in one step: a waterfall. Or it can flow down in small steps, with a network of cascades falling into ponds, interlinked by channels. Some channels run sideways into more ponds, and the network spreads over the slope. Sometimes work is done to pump water uphill into a higher pond. At the end, the result is the same, the water ends up in the lake.

In a cell, the chemical gradient is split into small steps through a network of chemical reactions. Products from one reaction are reactants or catalysts for others. Some of them form nanoengines which drive reactions against equilibrium. At the end, heat along with carbon dioxide, water and other molecules are dumped into the environment.

Many aspects of the wild complexity of living cells remain poorly understood. Despite this, thermodynamics can be used to clarify cell function at every level and this is the focus of the next chapters. Let’s start by investigating the nature of the environment inside cells.

1 Down at the Bottom

I take this title from Feynman (1959), one of the first discussions of the possibilities of manipulations at a molecular level.

The term nanoscale is loosely used to referred to processes which happen at a molecular level. A nanometre (nm) is 10⁻⁹ m. For comparison, a hair has a diameter of around 0.1 mm or 10⁵ nm; a sharp pin might have a point of 0.01 mm or 10⁴ nm. The smallest bacteria are a few hundred nm in length, the DNA double-helix has a diameter of around 2 nm and a water molecule is 0.3 nm long.

The molecular storm dominates behaviour at the nanoscale. Chapter 7 showed how it drives chemical reactions. It also affects every aspect of cells’ function. To get an idea of the magnitude of the effect, let’s jump ahead a bit and take the example of a nanomachine that performs some function in the cell. It turns out that the power exerted on the nanomachine by the molecular storm is a hundred billion times the power used by the machine. To put this in perspective, think of a person walking on a windy day. For them to feel the same relative force, the wind would need to blow at around 40,000 km/hour.³ To complete the analogy, this wind would blow from constantly changing directions. Cellular nanomachines must not only to be robust to this constant bombardment but somehow exploit its energy to carry out their functions.

A consequence of the molecular storm is that cells and their contents are always at thermal equilibrium. If heat is released by some process, it will be instantaneously dissipated, picked up as kinetic energy by the surrounding molecules. This means that thermal gradients cannot play an important part in the inner workings of cell. It also means that heat produced by one chemical reaction cannot be used to drive another.

Biochemistry textbooks often refer to a class of molecules called energy carriers. The idea is that such molecules undergo reactions that release energy, then this energy is used to drive other reactions against equilibrium. But this cannot happen. Thermal equilibrium at the nanoscale means heat produced diffuses away too fast to be able to perform any useful role. There is no way to capture the heat.

Another strange aspect of behaviour at the nanoscale is motion. Movement is a balance between inertia and viscosity. A person swimming can take a stroke and glide for a few meters before water resistance slows them down. Put on a wing-suit, jump off a high place and you can glide for miles. This is quantified by the Reynold’s number, the ratio of inertial to viscous forces. When the number is small viscous forces dominate. When it is large, inertial forces are more important. The larger the Reynolds number, the longer you can glide for.

For a person swimming in water, the Reynold’s number is large (10⁶).⁴ This means inertial forces dominate so gliding is possible. Imagine instead you were swimming in a more viscous liquid, say treacle (Reynolds number 10). The first half of a stroke would move you a bit forward, the second half would move you the same amount backwards. Overall, you wouldn’t move anywhere. For a bacterium in water, the Reynolds number is 10^–5: viscous forces dominate to an extent that inertia is irrelevant. This means motion is determined purely by the forces acting in the moment; the past, via inertia, has no effect.

Inside cells, the combination of the molecular storm and high viscosity has important implications for how nanoscale devices work. An influential article on the topic by a master of the field is entitled “Design principles for Brownian molecular machines, how to swim in molasses and walk in a hurricane”.⁵

A further fascinating feature of the nanoscale is only there do various different types of energy have approximately the same magnitude. This is shown in Fig. 9.2. The lines show electron binding energy (purple); thermal energy (yellow); two measures of mechanical energy (blue and green), an estimate of the electrostatic energy holding a protein in its folded shape (orange) and the energy in various chemical bonds (the red square, triangle and circle). Only at the nanoscale (the grey shaded area) do they all have roughly the same magnitude so can be readily interconverted. This means that a nanomachine can in principle harvest thermal energy from the molecular storm and use it to create chemical bonds, do mechanical work or produce electrical energy. This would not be possible at smaller scales (where binding energies are far larger than thermal) or at larger scales (where mechanical and chemical energies are much higher than thermal).

Fig. 9.2

Energy magnitudesFootnote

Reproduced from Phillips and Quake (2006), https://physicstoday.scitation.org/doi/10.1063/1.2216960, with the permission of AIP.

2 A Crowded Place

If you take all the components of a cell, drop them in a test tube and give it a good shake not much will happen. There are many reasons for this. One of them is that the interior of a cell is a very different environment from a test tube. It is jam-packed with large molecules which take up from 20 to 50% of its volume and constitute around a third of its mass. This is called macromolecular crowding. Figure 9.3 is an illustration of Escherichia coli, E. coli, a model bacterium. Take a while to scan the rich detail in this image. The following chapters discuss some of the structures that you see. In Chap. 14, I will discuss the figure in more detail.

Fig. 9.3

E. coli: macromolecular crowdingFootnote

Source https://pdb101.rcsb.org/sci-art/goodsell-gallery. By David S. Goodsell, RCSB Protein Data Bank. License: Creative Commons Attribution 4.0 International (CC BY 4.0).

A back of the envelope calculation confirms this. E. coli has a volume of around 10⁹ nm³. One of the largest nanomachines in the cell is called a ribosome. I’ll talk about these more in Chap. 13, but for the moment all that matters is that they are around 20 nm in diameter so have a volume of 30,000 nm³. If there are 10,000 ribosomes per cell, this means that ribosomes take up 30% of the cellular volume. If we repeat the calculation for the other macromolecules, the cell starts to seem very crowded indeed.

How does this crowding affect chemical reactions? In general, there are two obstacles to any reaction: the reactants need to be close together, think of this as a process of search, then they need to have sufficient energy to overcome the energy barrier. There are implications for both.

Crowding will slow down the rate at which large molecules diffuse through the cell interior so it might be expected to slow down the search process. However the dynamics of crowding are complicated and among the numerous effects are two that tend in the opposite direction. Firstly, even if molecules take longer to meet each other, they also spend longer close to each other increasing the probability they will react. Secondly, slower diffusion can actually increase the efficiency of the search. The intuition behind this is complex, but there is no particular reason why the random walk of Brownian motion should be the most efficient search algorithm. The upshot is that while search with crowding will be slower, it may also be more reliable.

The volume occupied by macromolecules is unavailable to other molecules. This effect increases with the size of the molecule. If two large molecules are separated by a bit less than their own diameter, a smaller molecule can easily pass between them whereas another large molecule cannot. So crowding doesn’t much change the molecular storm but large molecules are crunched together increasing their effective concentrations and so changing reaction rates and equilibria.

Also, crowding reduces the number of states available to the system so reduces its entropy. If two of the macromolecules bind, this will decrease their volume, increase the number of states available to the system and so will increase entropy. This extra entropic kick encourages molecules to combine, just as the hydrophobic effect drives lipids to form vesicles. The effect will be larger the larger the molecule and can range from a factor of 3 for a small protein to 10,000 for a larger structure.

Living systems are without exception crowded at a molecular level and crowding plays a role in all cellular processes and particularly in the way different processes interact. An important question for theories of the origin of life is how crowding could develop from the low concentrations typically found in water-based environments.

3 The Cell Membrane

The cell membrane separates a cell from its environment. The basic structure is a lipid bilayer, just like the vesicles described in the last chapter. Its physics is complex and a field in its own right, membrane biophysics.

In Fig. 9.3, the green part represents the membrane. If you look closely you’ll see a whole zoo of complicated structures embedded in it. Some on the inside, some on the outside and some linking outside to inside. These structures make up around half the membrane’s weight. They include components of the electron transport chain (see Chap. 12); mechanisms to actively transport molecules, either inward to eat, or outward to excrete; sensory devices producing chemicals which regulate the cells function according to outside conditions; and propulsive nanomachines, in this case a glorious flagellum and its attached motor.

It might seem trivial, but the membrane performs a more general role. It separates outside from inside. This has implications for thermodynamics. Restricting the contents of the cells to a limited volume reduces their entropy. One estimate⁸ suggests that it is the most important contribution to the entropy of cells. There are also philosophical implications. The membrane creates the separation between outside and inside that is the lowest-level definition of an individual.

4 Monomers and Polymers

Cells contain four main families of small organic molecules: nucleotides, amino acids, sugars and fatty acids. Although these small molecules, or monomers, play important roles in their own right, the main building blocks of cells are chains of monomers called polymers. There are four types of polymers: nucleic acids are chains of nucleotides, proteins chains of amino acids, polysaccharides chains of sugars and lipids chains of fatty acids.

I’ll run through the four types in the next subsections, but while I do so there’s an important point to keep in mind. For sugars and lipids, the order of the monomers doesn’t matter (they are mostly of just one type) so they can be produced by ordinary chemistry. For nucleic acids and proteins, the order is critical. To produce such ordered structures, nanoengines are needed.

Nucleic Acids

Nucleotides have three components, a base, a sugar and one or more phosphate groups. The base is a ring containing both carbon and nitrogen atoms. There are five bases: uracil, cytosine, thymine, adenine and guanine.

When a base and a sugar bond, the resulting molecule is known as a nucleoside (note the “s”). Nucleosides use ribose as the sugar, either in its standard form or as deoxyribose, with one less oxygen atom. A nucleotide (note the “t”) is formed by adding one or more phosphate groups to a nucleoside. A phosphate group consists of an atom of phosphorous bound to four atoms of oxygen, PO₄³⁻ usually simply written as P_i for inorganic phosphate. Phosphate plays diverse roles in cells, a 1987 article entitled “Why nature chose phosphates”⁹ argues this is due to its unique range of chemical properties.

As an example of a nucleotide, take adenosine monophosphate (AMP). It is made up of the base adenine, joined to a molecule of ribose to give the nucleoside adenosine then joined to a phosphate group. If another phosphate group is added we have adenosine biphosphate (ADP); adding a third gives adenosine triphosphate (ATP), which, as will soon see, is central to cellular processes. The reactions can be written as:

$$AMP + {P}_{i} \leftrightharpoons ADP + H_{2} {O}, \Delta G>0$$

$$ADP + {P}_{i}\leftrightharpoons ATP + {H}_{2} O, \Delta G>0$$

The link between nucleoside and phosphate happens by the elimination of a water molecule, known as a condensation reaction. The reverse reaction, involving the addition of a water molecule, is known as a hydrolysis. In water, equilibrium of both reactions will lie on the left. See Box 9.1 for further details.

Box 9.1: Condensation and hydrolysis

Condensation is a chemical process by which two molecules are joined together losing a molecule of water in the process. To illustrate this, take a molecule A with a hydrogen group attached to it (A–H) and another molecule B with a hydroxyl group (B–OH). Then the condensation reaction that joins them can be written:

$$A-{H} + B-{OH} \to A-B + {{H}}_{2}{O}$$

Hydrolysis is the reverse process by which a molecule is split by the addition of a water molecule:

$$A-B + {H}_{2} {O} \to A-{H} + B - {OH}$$

In water, the equilibrium of the second reaction will lie on the right. Trying to make a condensation reaction happen when there is an abundance of water is, in Nick Lane’s words, “like trying to wring out a wet cloth under water”.¹⁰ This means that if polymers are to form either the reaction needs to be driven away from equilibrium or it has to happen in an environment which excludes water molecules. This constrains cellular processes in interesting ways.

Nucleotides can link together to form chains called nucleic acids. Ribose nucleic acid (RNA) is formed from nucleotides consisting of the sugar ribose, one of the four bases adenine, guanine, cytosine or uracil and a single phosphate group. In deoxyribose nucleic acid (DNA), the sugar is deoxyribose and the base uracil is replaced by thymine. The chain consists of alternating sugars and phosphate groups. When an extra nucleotide is added to the chain, the phosphate group at the end of the chain bonds to the hydroxyl group of the sugar in another condensation reaction.

Proteins

Amino acids consist of two or more carbon atoms linked together in an unbranched chain. At one end of the chain is an amine group (−NH₂), at the other a carboxyl group (–CO₂H). Attached to the carbon chain are one or more side chains. The side-chain gives the amino acid its name and determines its properties, small or large, acid or base, hydrophilic or hydrophobic, polar or nonpolar. There are around 500 naturally occurring amino acids. Of these, 20 are used by cells. Table 9.1 gives a list of them. There’s no need to worry about the names; the point of this table is to show the diversity of their properties.

Table 9.1 Amino acid propertiesFootnote

This is adapted from https://en.wikipedia.org/wiki/Proteinogenic_amino_acid.

Amino acids join to form chains called peptides (if the chains are short, less than 20 or so amino acids) or proteins (for longer chains). The link happens by the carboxyl group (–CO₂H) at the end of one backbone joining with the amino group (–NH₂) at the end of other to form a peptide bond, again through a condensation reaction. Proteins in cells are between 50 and 2,000 amino acids long. They are by far the most complex known molecules.

Sugars and Lipids

Now for sugars. The simplest sugars are monosaccharides with the general formula (CH₂O)_n where n can have values between 3 and 8. In aqueous solution, the molecule forms a ring of six carbon atoms with hydrogen (C–H) and hydroxyl (C–OH) groups hanging from it. Glucose is a monosaccharide with n = 6. Monosaccharides can link together to form linear or branching chains. Chains of less than 10 monosaccharides are called oligosaccharides, longer chains are polysaccharides. For example, glycogen is a branching chain of from 2,000 to 60,000 glucose monosaccharides. Monosaccharides are linked via their carbon atoms again by means of a condensation reaction.

Lipids are the fourth type of molecule. I discussed their properties briefly in Chap. 8 and there’s no need to go into further detail.

In terms of composition, a cell is roughly 70% water. Of the remainder, 55% is protein, 20% RNA, 10% lipids and 3% DNA. The remaining 12% accounts for all the other types of molecule.

5 Folding

Proteins are long, flexible chains of amino acids. Most spontaneously fold into complex 3-dimensional shapes and it is these shapes which allow them to perform useful functions in the cell. An example is shown in Fig. 9.4. This is hexokinase, a protein which functions as a ratchet during the first step of the path which transforms glucose. At the top right of the figure are molecules of ATP and glucose to give scale. The protein is synthesised as a long chain of around 1,000 amino acids, then folds into the shape shown in the figure. What determines this shape?

Fig. 9.4

A folded proteinFootnote

Source https://en.wikipedia.org/wiki/Protein. Public domain.

The first factor is the properties of the amino acids forming the chain. Table 9.1 showed how they vary by mass, volume and the extent to which they are polar, acidic or hydrophobic. The order of amino acids is key: swap the position of two of them and the protein will fold into a different shape.

Central to the folding process is the hydrophobic effect. Just as in the case of lipids (see Sect. 8.4), a protein will become more stable if it folds to keep its hydrophobic parts on the inside and the hydrophilic parts on the outside. Macromolecular crowding gives an extra kick to this by encouraging molecular configurations with smaller volumes.

Then there are the properties of chemical bonds. The peptide bond, joining individual amino acids in the chain, does not allow rotation. However other carbon–carbon and carbon–nitrogen bonds can rotate. Weak bonds form between different parts of the polypeptide backbone, between the backbone and side chains and between different side chains. Different amino acids will have different affinities for the different types of weak bond.¹³ While these bonds are a couple of orders of magnitude weaker than the covalent bonds which hold molecules together, many of them are formed. Their combined strength holds the protein in a particular shape.

Even a simple protein can potentially fold into a VAST number of different shapes. To get an idea of the numbers involved, take a protein consisting of 100 amino acids each of which can adopt 2 states. Then there are 2¹⁰⁰ or 10³⁰ configurations. For realistic proteins consisting of many more amino acids each of which can adopt a many different states, the number of configurations will be VAST. Among all these possibilities, only one shape, called the native state, will allow a protein to carry out its chemical function in the cell. If we start with an unfolded protein, how does it find this unique shape among all these countless possibilities?

Clearly it cannot get there by random search, there is just not enough time (this is known as “Levinthal’s paradox”). Instead, evolution has selected proteins for which the native state represents a unique minimum of energy. Folding can then be thought of as the movement down a funnel, starting with the unfolded protein at high energy and proceeding down the funnel to states of progressively lower energy. The left panel of Fig. 9.5 gives a stylised illustration. A grain of sand rolling down a physical funnel can take many different routes depending on the properties of the funnel but always ends up in the same place. Protein folding is convergent in the same sense. Since the native state is minimum energy, a protein can reach it by an endless number of routes.

Fig. 9.5

The protein folding funnelFootnote

Source Dill and Chan (1997), https://www.nature.com/articles/nsb0197-10. Reproduced with permission from Springer Nature.

The molecular storm drives the protein down the funnel. The constant impacts displace the protein’s component molecules and twist its bonds. Impacts causing structural changes that increase the protein’s energy will tend to be transient, those that reduce it will tend to be persistent. So the process pushes the protein down the funnel, to states of progressively lower energy.

Folded proteins are low entropy equilibrium structures, just like the crystals of Sect. 5.2. Each step down the funnel dissipates heat into the environment, increases overall entropy and increases the stability of the folded protein.

When thinking about proteins, it is vital to remember that they are not random sequences of amino acids but instead ones that have been selected over billions of years. What matters to the survival of the cell is that proteins functions reliably. So evolution will select proteins which fold robustly. Indeed, a 2008 article¹⁵ suggests this is the most important factor in the protein selection. Evolution will also select proteins which are robust to errors so that if one amino acid is substituted for another there is not too much effect on function.

DNA and RNA can fold in similar ways. The resulting three-dimensional structures are just as central to the functions of the cell.

6 Genetic Information

Life depends on the ability of cells to store and use information. In all existing organisms, genetic information is encoded in DNA.¹⁶ A single strand of DNA consists of a backbone of sugar molecules alternating with phosphate groups. From each sugar molecule hangs one of four bases: adenine, thymine, cytosine and guanine (A, T, C and G). The bases differ both in size and the number of hydrogen bonds they can form. The bases A and G are larger, consisting of two carbon-rings; T and C are smaller, consisting of only one. A and T have two sites for hydrogen bonds whereas G and C have three. The order of the bases encodes information in this language of 4 letters, A, C, G and T.

In cells, DNA molecules take the form of a double helix consisting of two such strands, linked by hydrogen bonds between the bases. Four effects determine the shape of the molecule. Firstly, for the two strands to be parallel, a large base must always pair with a small base. Secondly, the lowest energy state will involve all hydrogen bonds being used, i.e. the bases that form 3 bonds pair with each other. These taken together mean the most stable pairs will be A–T and G–C. If this were all that was going on, the resulting polymer would be 2-dimensional with the two parallel backbones lying flat in the plane and linked by the bases, as at the top of Fig. 9.6.

Fig. 9.6

The double helixFootnote

Source https://en.wikipedia.org/wiki/DNA. Public domain.

However further effects determine a more complex 3-dimensional structure. The bonds linking the molecules in the backbone are neither perfectly flexible nor perfectly rigid but instead have a number of preferred angles. To see how the double-helix arises, imagine building a DNA molecule from its individual paired nucleotides, progressively adding either A–T or G–C. Each time you add a new pair, the bond linking the two sugars is angled at around 36° (the minimum energy configuration in an aqueous environment). Add another pair and there’s another 36° twist. Add 8 more pairs and the total twist is around 360° i.e. the next pair will have the same orientation as the original one. This is shown at the bottom of the figure. The structure will be stabilised by the hydrophobic effect since it packs the non-polar bases in the inside of the molecule with the polar backbones on the outside. This helix, with a full turn every 10 pairs or so, is the form occurring in all life and is known as B-DNA. Other forms are possible, for example under dehydrating conditions the helix is looser repeating every 12 pairs, called A-DNA.

RNA can encode the same information as DNA, with the base thymine replaced by uracil. In cells, RNA usually exists as single strands.¹⁸ These strands can fold into complex shapes and play similar roles to proteins. This combination of functions is unique and has important implications when thinking about the origin of life.

Molecules of DNA are equilibrium structures par excellence. Erwin Schrödinger knew this was a necessary quality when he famously predicted their existence a couple of decades before their discovery, describing them as “aperiodic crystals”.¹⁹

7 Assembly

Cells contain a host of complex structures built from macromolecules. Their ability to carry out their function depends on their parts being precisely assembled. Rather than controlling every step in this process directly, cells delegate it to physics. Think of a hanging a saucepan from a hook. Instead of having to secure it, you can depend on gravity to hold it in place.

We’ve already seen examples of self-assembly: lipids forming vesicles or the folding of proteins. Now let’s take an example involving the assembly of several macromolecules into a nanoengine, specifically ATP synthase, of which we’ll hear much more in Chapter 12. Figure 9.7 gives an overview of the process.

Fig. 9.7

Assembling an engineFootnote

Source Vu Huu et al. (2022). https://www.nature.com/articles/s41467-022-28828-1. License: Creative Commons Attribution 4.0.

In the box at the top left are the components or subunits, five different proteins labelled with the Greek letters alpha through epsilon. The smooth shapes make it easy to forget that each of the subunits is itself a large protein. For example, the alpha (α) subunit is made up of around 500 amino acids, folded into the complex shape shown in Fig. 9.8.

Fig. 9.8

The alpha subunitFootnote

Source https://en.wikipedia.org/wiki/ATP5F1A. License: Creative Commons Attribution-Share Alike 3.0 Unported.

The complete engine is shown at the bottom right. It is made up of, three alphas, three beta and one each of the others. Both the orientations of each protein and their order matter. Swap an alpha for a beta, and the engine won’t work.

How the assembly happens is breathtaking in its simplicity. The various proteins are built in large numbers (the process is described in Chap. 13) and released into the inside of the cell. Here they experience the full force of the molecular storm, which constantly reorients them and brings them into contact with other large molecules. Sometimes an alpha and a beta will collide with just the right orientation so that intermolecular forces can bind them together. If at the same time a molecule of ATP is present, this will lock the two proteins together.²² If instead the alpha and beta collide with the wrong orientation, or in the absence of ATP, they will not assemble. The diagram shows how similar processes, some involving ATP and some not, result in the complete engine.

Think of the crowded interior of the cell as a mass of components, constantly being shaken up by the molecular storm trillions of times every second. Most collisions will not result in binding, but enough do to produce the structures the cell needs to continue functioning. This randomness underlies all cellular processes. I will return to the more general implications of this in Chap. 14.

Proteins fold reliably because they have been selected by evolution to do so. The same is true of the self-assembly of nanoengines. A nanoengine is no use if it doesn’t assemble correctly. There will be strong selective pressure for nanoengines that assemble reliably so the processes we observe are necessarily robust ones. In thermodynamic terms, these are all equilibrium structures. Recent work gives important insights into how thermodynamics impacts their evolution. The process is called dissipative adaptation and I’ll discuss it in the context of the origin of life in Chap. 15.

8 A Chemical System

Let’s now take a step back. I started this chapter with a description of a cell as a chemical system which uses a chemical gradient to divide into two cells. Everything that happens in between is called metabolism. Figure 9.9: is a flowchart representation of the system. Its aim is to introduce the different parts of metabolism and the relation between them and provide a reference for the chapters that follow.

Fig. 9.9

A chemical system

Rectangles represent processes, sub-networks of chemical reactions; ellipses represent types of molecules. At the top left of the diagram are the food molecules. At the top right, matter and energy are dissipated into the environment. At the bottom right the cell creates a copy of itself. So far, it’s a copy of Fig. 9.1. Let’s now unpack some of what happens inside the cell.

At the top left is central metabolism. This is a set of reactions which uses food molecules to activate carrier molecules (of which more in the next chapter) and produce useful chemical components, among them carbon skeletons which form the basis for more complex molecules. Following along to the right, some of the activated carriers enter a process called the electron transport chain and are transformed into ATP, the most general-purpose carrier molecule. ATP and other carriers are used by many of the reactions that constitute the cell.

Moving down the left, the carbon skeletons are raw materials for a process called biosynthesis, a set of reactions which produce molecules which other process use: amino acids, nucleotides, lipids and polysaccharides (not shown on the diagram).

Now moving over to midway up the right, a process called transcription copies the genetic information in DNA into RNA. Then a process of translation assembles amino acids into proteins according to the sequences specified by the RNA. These proteins then fold and act as enzymes. At the bottom right are the two processes which lead to the cell reproducing. The first is DNA replication, which makes a second copy of the genetic information. The second is cell division, which makes a second copy of the rest of the structure of the cell. In combination, they produce a copy of the cell.

The diagram is an extreme simplification. Despite this, I hope the figure is a useful overview; keep it in mind during the following chapters.

Throughout this chapter, I’ve used the term cell without being more specific. The system described in this and the following chapters corresponds loosely to the simplest free-living bacterium (“free-living” to exclude parasites which can be simpler since they delegate functions to their host). However, to find clear examples and good data I am usually forced to draw on studies of the well-known E. coli, a far more sophisticated beast. Since I am discussing general mechanisms, I don’t think this matters.

Apart from describing an actual cell, this set of properties is interesting for two other reasons. They are similar to the set of properties shared by all known life. You can think of them as a core, around which more complex cells wrap additional layers. Further, they are (arguably) similar to the properties of the last universal common ancestor of all life on earth.

9 Further Reading

Molecular biology textbooks cover much of the material in this chapter. My favourites are Alberts et al. (2022) and Kim and Gadd (2008). A more technical work, focussing on thermodynamics, is Kurzyński (2006).

The standard description of the viscous nanoscale environment and its consequences is in Purcell (1977); for molecular crowding, see Ellis (2001); for a review of membrane biophysics, see Zimmerberg (2006); for the entropy of cells, Marín et al. (2009); for the role of phosphates, Kamerlin et al. (2013); for self-assembly, Whitesides and Grzybowski (2002).

A full list of sources can be found on www.TheMaterialWorld.net.