Structural materials in cells
Structural materials in cells

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Structural materials in cells

2 Construction with lipids

The cell membrane is constructed from lipids. Chemically, lipids are a rather varied group of compounds that include all the substances you might already think of as fats or oils. What they have in common is that they are all insoluble in polar liquids like water, but soluble in organic (carbon-based) solvents: by this I mean the sort of smelly solvents you tend to find in paints, glues and degreasing agents; chloroform is one example. Lipids make up the fatty components of living organisms and are the major components of margarine, cooking oil, butter and the white fat associated with meat. The terms ‘fat’ and ‘oil’ simply describe whether a lipid is solid (a fat) or liquid (an oil) at room temperature. Fats and oils are important in cells as energy storage compounds, while the cell wall itself is constructed from a class of lipids known as phospholipids.

The reason for their insolubility in water is that lipids contain large hydrophobic groups. Hydrophobic literally means ‘water-hating’ and generally applies to non-polar substances or chemical groups. In contrast, polar substances or groups are termed hydrophilic or ‘water-loving’. As the name suggests, they have an affinity for water and are more likely to dissolve in it.

The interplay between hydrophilic and hydrophobic groups is important in many biological materials.

Their hydrophobic nature means that lipids tend to separate from water and from all water-soluble, hydrophilic compounds and to group themselves together as large hydrophobic aggregates, held together by weak hydrophobic interactions. This is why oil and water don't mix. Because of the weak bonding between the molecules, lipids tend to be fluid aggregates that can easily change shape. Think of a lump of lard: if you press on it, it dents. A material like this with a certain amount of fluidity can be extremely useful in certain situations. Insolubility in water is also a useful property when it comes to forming a barrier to keep some substances separate from others.

Many important lipids, including the phospholipids that make up cell membranes, contain both hydrophobic and hydrophilic groups. Such molecules are termed ‘amphiphilic’ and exhibit particularly interesting properties when mixed with water. Figure 2 is a sketch representing an amphiphilic lipid molecule, such as a phospholipid. The two ‘tails’ are based on chains of carbon atoms and are hydrophobic. The head is a polar hydrophilic group. Other lipids may have a different number of tails.

Figure 2
Figure 2 Simple representation of a lipid molecule. This one has two hydrophobic (water-hating) tails and a hydrophilic (water-loving) head, like a phospholipid

Consider how amphiphilic lipid molecules might aggregate together in a strongly hydrophilic, watery environment. The hydrophobic chains will avoid water, coming together and interacting with one another on the inside of the aggregate. This leaves the hydrophilic head groups on the outside of the aggregate, in contact with water molecules. The charged head groups will repel each other to some extent, so the arrangement they adopt must achieve a balance between the attractive forces (between the heads and the surrounding water) and the repulsive forces (between neighbouring heads). A wide range of structures can be produced, depending on the shape of the molecule, the nature of the head group, and the concentration of the mixture. Some examples are shown in Figure 3.

Figure 3
Figure 3 Cross sections of some of the common structures adopted by amphiphilic lipids in water: (a) micelle; (b) inverted micelles; (c) bilayer; (d) bilayer vesicle, or liposome

The formation of well-defined structures by amphiphilic lipids is the first of several examples we will see of self-assembly, which is a key feature of many natural systems. Self-assembly means that no outside influence is needed to cause the molecules to organise in a particular way: it is a direct consequence of their molecular design and the electrostatic forces that exist, on very small scales, between individual molecules. It relies on Brownian motion to shake the molecules around so that the optimum arrangement can be found.

Some authors would describe the behaviour of lipids as self-organisation, since there is more than one possible way of arranging the molecules, and reserve the term self-assembly for more specific interactions such as those found in proteins. Here, I will not differentiate between the two and only the term self-assembly will be used.

Amphiphilic lipids, which contain a polar, water-soluble group attached to a non-polar, water-insoluble hydrocarbon chain, have many uses. They are widely used as surfactants (substances that reduce the surface tension of a liquid) and emulsifiers (substances that promote the formation of a stable mixture of oil and water), and you'll find plenty of examples around the home. Soaps and detergents work by forming micelles when added to water; see Figure 3(a). These micelles are able to surround non-polar contaminants such as grease, encapsulating them within their hydrophobic core and thus allowing them to dissolve in water, as illustrated in Figure 4. The charged heads on the surface ensure that the micelles repel one another, preventing them from clumping together – effectively emulsifying the dirt. In other circumstances (higher concentrations, or differently shaped lipids) the micelles may be inverted, as in Figure 3(b). In this case the hydrophilic heads point inwards, surrounding small globules of water within a matrix of lipids.

Lipids are also common in the kitchen. Many foodstuffs contain both oil and water, and a variety of emulsifiers are used to stabilise their structures. For example, lipids found in egg yolk act as an emulsifier in egg mayonnaise, enabling a stable emulsion to be formed from oil and vinegar.

Figure 4
Figure 4 Dirt surrounded and made soluble by lipids

The double-layered lipid structure shown in Figure 3(c) illustrates the basic arrangement of the phospholipids in a cell membrane. A more detailed view is given in Figure 5. (Plant cells possess a tough outer cell wall in addition to the phospholipid membrane. Here we will concentrate only on the membrane itself.) Within the membrane the phospholipids cluster together to form a sheet-like structure, with all the hydrophobic tails in the centre, screened from the surrounding water. The phospholipid bilayer of a cell membrane is a very effective barrier, preventing hydrophilic molecules from passing freely into, or out of, the cell. Membranes also define the boundaries of structures within cells, restricting various cellular functions to particular compartments of the cell. Another important function of the membrane is to support other molecules, which allow the cell to interact with its neighbours and with the external environment. Larger molecules, such as proteins, ‘float’ within the fluid lipid bilayer; we'll return to consider these later.

Figure 5
Figure 5 A biological membrane; a typical membrane thickness is about 10 nm. The green structures are membrane proteins; some of these traverse the membrane and others are on its surface

The final structure illustrated in Figure 3 shows a lipid bilayer bent round on itself to form an enclosed compartment. These structures may be described as liposomes or vesicles, depending on the context. (The term liposome tends to be used for synthetically produced bilayer structures. The term vesicle is used more generally, but has a specific meaning within cells as a small spherical bilayer sac in which substances are transported or stored.) The bubbles formed by soaps and detergents also have a bilayer structure similar to that in Figure 3(d) and provide us with a reasonable model for a cell membrane. Blowing a bubble shows us how a flexible membrane can be bent round on itself to form an enclosed space; you can demonstrate the fluid and self-sealing nature of a membrane by moving an object, such as a pencil, through a soap film and then removing it.

Liposomes can be used to encapsulate water-soluble substances such as vaccines, drugs, enzymes or vitamins and deliver them to different cells in the body. Drug-delivery systems based on lipids are under development and show considerable potential. Elsewhere, aggregates of lipids in solution are being used to produce nanoparticles of precisely controlled size and shape, such as the quantum dots available for molecular labelling. Langmuir-Blodgett films (named after the scientists who first studied them) provide a well-established method of generating structures built up from lipid mono layers that have potential for electronic applications.

Box 1 Langmuir-Blodgett films

A Langmuir-Blodgett (LB) film is made up of highly organised layers of lipids, each just one molecule thick, deposited onto a solid substrate by repeatedly dipping it into a water bath with a lipid film floating on top. By varying the experimental conditions and the lipid used, multilayer stacks can be built up with precisely controlled molecular compositions. LB films may consist of a single layer or many, up to a depth of several micrometres, and can be made with various electrochemical and photochemical properties. They are being investigated as possible structures for tiny integrated circuits.

Synthetic bilayer sacs like those in Figure 3(d) are relatively easy to make and provide a reasonable model for a (very!) simple cell. But for many nanoengineering applications it is much more useful to have a lipid layer that is tethered in a fixed position. Fixed bilayer membranes supported on solid surfaces are much more stable and often offer a more promising route for the development of structures that mimic nature.

In related developments, the self-assembling properties of lipid-like molecules containing thiol groups have been used in microcontact printing and dip-pen lithography to produce self-assembled features on gold surfaces at scales as small as tens of nanometres. (Thiol groups, which contain sulphur and hydrogen, are particularly useful for ‘sticking’ biological molecules to metal surfaces.) By varying the chemical structure of the molecules used, the surface chemistry can be modified so that the thiol may function as an etch resist or produce a surface with markedly different properties in different areas.


  • (a) What do the four structures in Figure 3 have in common?

  • (b) If salt (sodium chloride, Na+Cl) were added to the mixture in Figure 3(a), where would it go? What about petrol (which contains hydrocarbon chains, such as C8H18)?


  • (a) In all the structures the hydrophilic heads of the lipids are in contact with the water, while the hydrophobic tails are not.

  • (b) The salt would dissolve in the water surrounding the micelle. Petrol is hydrophobic, and would mix with the lipid chains in the centre of the micelle.


Suggest which of the structures shown in Figure 3 would be suitable for the following applications:

  • (a) restricting the size of crystals growing from solution in water

  • (b) suspending a hydrophobic pigment molecule in a water-based paint

  • (c) providing a boundary between an area of high concentration and an area of low concentration within a liquid

  • (d) delivering a water-soluble vitamin to a cell.


  • (a) For this we need an enclosed compartment within which the crystals can grow. Inverted micelles would provide this, and the size of the cavity can be varied by choosing different lipids. Although liposomes also provide compartments, crystals of other sizes could grow from the surrounding liquid.

  • (b) Micelles are able to surround the hydrophobic molecules and render them soluble.

  • (c) The bilayer would be most suitable here; concentration gradients across lipid bilayers are very common in cells.

  • (d) Here a liposome/vesicle-based delivery system could be used, with the vitamin enclosed within the lipid compartment.

The principles that govern the self-assembly of lipids can also be applied if we take small units with different chemical characteristics and join them together. This is the situation that exists in a block copolymer, as described in Box 2 Self-assembly in block copolymers.

Box 2 Self-assembly in block copolymers

Block copolymers have chains made up of alternating sequences of two or more different repeating units. Let's assume that there are just two components, which I'll call A and B, so that a section of chain might look something like this:

Now suppose that the A units are hydrophilic and the B units are hydrophobic. The As will try to separate from the Bs and clump together, and vice versa, leading to phase separation on a tiny scale. The structures that can be produced are very similar to those obtained from lipids but, in this case, the result is a solid, with greater connectivity throughout the structure because the units are linked together in chains. Figure 6 shows the sort of structural arrangements that can be obtained. By changing the length and proportions of the different blocks, the microstructure, and hence the bulk properties of the material, can be finely controlled.

Figure 6
Figure 6 Examples of the different micro structures adopted by block copolymers with hydrophobic and hydrophilic elements

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