B2.1 Membranes and membrane transport

Saturated and unsaturated fatty acids

A membrane must be fluid enough to be flexible, let proteins move and allow vesicles to form, but strong enough not to break or leak. The fatty acid tails control this.

• Saturated fatty acids have no C=C double bonds. Their chains are straight, so they pack tightly together. They have higher melting points and make membranes stronger and less fluid at higher temperatures.
• Unsaturated fatty acids have one or more C=C double bonds. In membranes these are mostly cis double bonds, which put a kink in the chain. Kinked chains cannot pack closely, so they have lower melting points, and membranes rich in them stay fluid and flexible at the temperatures the cell experiences.

For example, stearic acid (18 carbons, saturated) melts at about 69 °C, while oleic acid (18 carbons, one cis double bond) melts at about 13 °C.

Adaptation to habitat

Organisms whose body temperature follows their surroundings adjust membrane composition to match. Fish living in polar seas, at temperatures close to 0 °C, have a higher proportion of unsaturated fatty acids in their membrane phospholipids than fish from warm tropical waters. This keeps their membranes fluid in the cold, whereas tropical fish have more saturated fatty acids, keeping membranes stable at higher temperatures. Even within one species, such as the goldfish, individuals acclimatized to cold water increase the unsaturated fraction of their membranes. Keeping fluidity roughly constant in this way is called homeoviscous adaptation.

Cholesterol

Cholesterol is a steroid found in animal plasma membranes. Most of the molecule is hydrophobic and lies among the fatty acid tails; its small hydroxyl (–OH) group is hydrophilic and sits next to the phosphate heads. Its rigid ring structure acts as a modulator (buffer) of fluidity:

• At higher temperatures it restrains the movement of the phospholipid tails, so the membrane is less fluid and less permeable to ions and small polar molecules.
• At lower temperatures it gets between the tails and stops them packing into a regular, solid arrangement, so it prevents the membrane stiffening.

A vesicle is a small sac of membrane surrounding a droplet of fluid. Vesicles can form from a membrane and fuse with one because the membrane is fluid: phospholipids are not covalently bonded to each other (they are held together by hydrophobic interactions), so the bilayer can bend, pinch off and reseal without tearing. The hydrophobic tails always stay away from water, so the membrane remains continuous at every stage. Large molecules and particles that cannot pass through membrane proteins are moved in this way. Both processes use energy from ATP.

Endocytosis

In endocytosis part of the plasma membrane folds inwards around material outside the cell. The edges meet and fuse, so a vesicle containing the material separates into the cytoplasm.

• Phagocytosis: white blood cells such as macrophages and neutrophils engulf bacteria in large vesicles, which later fuse with lysosomes so the bacteria are digested.
• Unicellular organisms such as Amoeba take in food particles in the same way.
• Cells in the placenta take up proteins, including antibodies, from the mother’s blood by endocytosis.

Exocytosis

In exocytosis a vesicle moves to the plasma membrane and fuses with it, releasing the vesicle’s contents outside the cell. The vesicle membrane becomes part of the plasma membrane.

• Secretion of proteins: exocrine (acinar) cells of the pancreas release digestive enzymes, and β cells in the pancreatic islets release insulin, from vesicles made by the Golgi apparatus.
• Neurotransmitter release: at a synapse, vesicles of neurotransmitter fuse with the presynaptic membrane.

Endocytosis removes area from the plasma membrane and exocytosis adds it, so a cell that grows can enlarge its plasma membrane by exocytosis of vesicles carrying new phospholipids.

Neurons control the movement of ions using gated channels: channel proteins that open only in response to a particular stimulus, letting a pulse of ions diffuse through before they close again. The two kinds required are neurotransmitter-gated and voltage-gated channels.

A neurotransmitter-gated channel: the nicotinic acetylcholine receptor

The nicotinic acetylcholine receptor is in the postsynaptic membrane at many synapses, including those between motor neurons and muscle. It is both a receptor and an ion channel: five protein subunits surround a central pore. (It is named “nicotinic” because nicotine also binds to it.)

1. Acetylcholine released from the presynaptic neuron binds to the receptor sites on the outer surface.
2. Binding causes a conformational change (change in shape) that opens the pore.
3. Positively charged ions, mainly Na⁺, diffuse through. Na⁺ moves into the cell down its concentration gradient and makes the inside less negative (depolarization).
4. Binding is reversible. When acetylcholine leaves the receptor (and is broken down), the pore closes.

Voltage-gated sodium and potassium channels

Voltage-gated channels open and close in response to changes in the membrane potential (the voltage across the membrane). They are responsible for nerve impulses.

• At the resting potential, about −70 mV, both channels are closed.
• If the membrane is depolarized to about −50 mV (the threshold), voltage-gated Na⁺ channels open and Na⁺ diffuses in, making the inside positive.
• At about +30 to +40 mV the Na⁺ channels close (inactivate), and voltage-gated K⁺ channels, which respond more slowly, are open. K⁺ diffuses out, returning the inside to a negative potential.

Both kinds are channels, so ions always move by facilitated diffusion, down their gradients. The gradients themselves are created by sodium–potassium pumps (next section). For how these channels produce action potentials and synaptic transmission, see C2.2 Neural signalling.

The sodium–potassium pump is an integral protein found in the plasma membranes of animal cells. It is an exchange transporter: in each cycle it moves two different ions in opposite directions, three Na⁺ out of the cell and two K⁺ into it, using one ATP. Both ions move against their concentration gradients, as Na⁺ is more concentrated outside and K⁺ is more concentrated inside.

The six stages

1. The pump is open to the cytoplasm. Three Na⁺ from inside the cell bind to it.
2. ATP is hydrolysed; a phosphate group attaches to the pump (phosphorylation) and ADP is released.
3. Phosphorylation causes a conformational change (change in shape), so the pump opens to the outside. Its affinity for Na⁺ falls, and the three Na⁺ are released outside.
4. Two K⁺ from the extracellular fluid bind to the pump.
5. K⁺ binding causes the phosphate to be released, and the pump returns to its original shape, open to the cytoplasm.
6. The two K⁺ are released into the cytoplasm, and the pump can bind Na⁺ again.

Importance in generating membrane potentials

The pump builds up and maintains concentration gradients of Na⁺ (high outside) and K⁺ (high inside) across the membrane. These gradients are the store of potential energy used by neurons:

• Each cycle moves three positive charges out for every two in, so the pump itself makes the inside slightly more negative.
• More importantly, the membrane at rest is more permeable to K⁺ than to Na⁺, so K⁺ diffuses out down its gradient. This leaves the inside negative relative to the outside, giving the resting potential of about −70 mV.
• During a nerve impulse, Na⁺ and K⁺ diffuse through voltage-gated channels down the gradients the pump created. The pump then restores them.

The same Na⁺ gradient also powers other transport, such as glucose cotransport.

Glucose is polar, so it needs a membrane protein to cross. In the cells lining the small intestine and the kidney tubule, glucose is moved into the cell even when its concentration inside is already higher. The energy comes not from ATP directly but from a sodium gradient. This is indirect (secondary) active transport.

How it works

1. Na⁺/K⁺ pumps in the membrane facing the blood use ATP to pump Na⁺ out of the cell. This keeps the Na⁺ concentration inside the cell low, so there is a steep Na⁺ gradient from the lumen into the cell.
2. A sodium–glucose cotransporter in the membrane facing the lumen binds Na⁺ and glucose together. In the small intestine this protein (SGLT1) binds two Na⁺ with each glucose.
3. The cotransporter undergoes a conformational change. Na⁺ moves into the cell down its concentration gradient, and the energy released carries glucose in against its gradient. The cotransporter does not use ATP itself; both substances move in the same direction, so it is a cotransporter.
4. Glucose leaves the cell on the blood side by facilitated diffusion through glucose transporter proteins (GLUT2), down its concentration gradient.

Where it matters

• Small intestine: epithelial cells of the villi absorb glucose from digested food, even when little glucose remains in the lumen, so almost none is lost in faeces.
• Nephron: cells of the proximal convoluted tubule reabsorb glucose from the filtrate using similar sodium-dependent cotransporters (mainly SGLT2), so normally no glucose appears in the urine. See D3.3 Homeostasis for the structure of the nephron.

If the Na⁺/K⁺ pumps stop, for example when respiration is inhibited, Na⁺ builds up inside the cell, the gradient is lost and glucose uptake stops, even though the cotransporter itself is unaffected.

In multicellular animals, cells are held together to form tissues. The binding is done by cell-adhesion molecules (CAMs): proteins in the plasma membrane with a part that projects into the extracellular space.

• The extracellular part of a CAM on one cell binds to a CAM on an adjacent cell. Many of these bonds together hold the cells firmly in place, forming a cell–cell junction.
• The intracellular part is often linked to the cytoskeleton, so the force is spread through the cell rather than tearing the membrane.
• Cells of the same type usually carry the same types of CAM, so they recognise and stick to each other, which helps sort cells into the correct tissues during development.

There are different forms of CAM for different types of cell–cell junction. Some junctions hold cells tightly together to resist mechanical stress, as in skin and heart muscle; others seal the gaps between epithelial cells so that substances cannot leak between them. CAMs work together with the carbohydrate chains of glycoproteins and glycolipids, which also contribute to cell adhesion and recognition.