Membrane transport

Downhill and uphill

The bilayer blocks ions and most polar molecules, so cells use proteins to move them. The key question for any transport process is which way the substance is going relative to its gradient.

A concentration gradient is a difference in concentration across the membrane. Molecules naturally spread from high concentration to low; that's moving "downhill", and it releases energy rather than costing it. Moving from low to high is "uphill", and it needs an energy input.

For ions there's a second force. The inside of a typical cell is negatively charged relative to the outside; this voltage is the membrane potential. It pulls positive ions in and pushes negative ions out. Concentration and charge together make up the electrochemical gradient, and it's this combined gradient that decides which way an ion runs downhill.

Passive transport: no energy needed

In passive transport, substances move down their electrochemical gradient, and the cell spends no energy. There are two kinds.

Simple diffusion is movement straight through the bilayer. It works for small nonpolar molecules such as O₂ and CO₂. The rate rises in proportion to the concentration difference: double the gradient and you double the rate.

Facilitated diffusion is movement through a transport protein. Channel proteins form water-filled pores that let particular ions or molecules through; many are gated, opening only in response to a signal such as a voltage change or a binding molecule. Carrier proteins bind their passenger, change shape, and release it on the other side. Channels are much faster, passing tens of millions of ions a second, while carriers manage about a thousand to a million molecules a second.

Carriers have a limit that channels and simple diffusion don't show so clearly. Each carrier can only move so many molecules per second, and there are only so many carriers in the membrane. At high concentrations, all of them are busy all the time: the carriers are saturated, and the rate levels off at a maximum. This is the same pattern you see when enzymes run out of free active sites.

Primary active transport: pumps that burn ATP

In active transport, a substance is moved against its electrochemical gradient, which takes energy. In primary active transport, that energy comes directly from ATP. The proteins that do it are called pumps. Skou's enzyme, the Na⁺/K⁺-ATPase (sodium–potassium pump), is the classic example. Here's one cycle:

1. 1The pump faces the inside of the cell, where it binds three Na⁺ ions.
2. 2It splits ATP and a phosphate group is attached to the pump.
3. 3The phosphate makes the pump change shape so it opens to the outside, where it releases the three Na⁺.
4. 4In this shape it binds two K⁺ ions from outside, and the phosphate group falls off.
5. 5Losing the phosphate flips the pump back to face the inside, where it releases the two K⁺. It's ready to start again.

Each cycle moves 3 Na⁺ out and 2 K⁺ in, so one positive charge leaves the cell every time. A pump that moves net charge like this is called electrogenic, and it helps keep the inside of the cell negative. The pump is expensive: a typical cell spends a large fraction of its ATP on it, often quoted as around 30%, and nerve cells considerably more (up to about 70%).

Secondary active transport: riding on another gradient

The Na⁺/K⁺ pump keeps Na⁺ much more concentrated outside the cell than inside. That gradient is stored energy, like water held behind a dam. Na⁺ "wants" to flow back in, and cells harness that urge.

In secondary active transport, a protein lets Na⁺ (or another ion) flow down its gradient and uses the energy released to drag a second substance up its own gradient. The cells lining your small intestine absorb glucose this way: a sodium–glucose symporter carries Na⁺ and glucose into the cell together, piling glucose up inside even when there's more glucose in the cell than in the gut.

• A uniporter carries one substance in one direction.
• A symporter carries two substances in the same direction.
• An antiporter carries two substances in opposite directions.

Bulk transport: moving things in vesicles

Some cargo is far too big for any channel or carrier: whole bacteria, large proteins, droplets of fluid. Cells move these in vesicles, and this also needs energy.

• Endocytosis brings material in: the plasma membrane folds inward around it and pinches off as a vesicle.
• Phagocytosis ("cell eating") engulfs large particles, such as bacteria taken in by white blood cells. The vesicle then fuses with a lysosome, which digests the contents.
• Pinocytosis ("cell drinking") takes in small droplets of extracellular fluid and whatever is dissolved in it.
• Receptor-mediated endocytosis is selective: only molecules that bind receptors on the cell surface are taken in. Cells collect cholesterol-carrying LDL particles this way; in the inherited disease familial hypercholesterolaemia the LDL receptors are faulty, so cholesterol builds up in the blood.
• Exocytosis works in reverse: a vesicle fuses with the plasma membrane and releases its contents outside. This is how cells secrete hormones and digestive enzymes, and how nerve cells release neurotransmitters.

Key terms

Electrochemical gradient

The combined effect of an ion's concentration difference and the membrane's voltage on its movement.

Passive transport

Movement down an electrochemical gradient with no energy input.

Facilitated diffusion

Passive transport through a channel or carrier protein.

Saturation

The levelling-off of transport rate when all carrier proteins are working at full speed.

Primary active transport

Movement against a gradient powered directly by ATP hydrolysis, as in the Na⁺/K⁺ pump.

Secondary active transport

Movement against a gradient powered by another ion flowing down a gradient that a pump built.

Symporter / antiporter

A carrier that moves two substances in the same direction / in opposite directions.

Electrogenic

Moving net charge across the membrane, as the Na⁺/K⁺ pump does (3 Na⁺ out, 2 K⁺ in).

Endocytosis / exocytosis

Taking material in by forming a vesicle / releasing it by fusing a vesicle with the membrane.

Check yourself

Try answering in your head before you open each answer.

• 1.Ouabain blocks the Na⁺/K⁺ pump. If intestinal cells are treated with ouabain, what happens to their uptake of glucose through the sodium–glucose symporter? Would the change be instant?Show answerHide

  Glucose uptake falls and eventually stops, because the Na⁺ gradient that powers the symporter is no longer being maintained. It isn't instant: the existing gradient keeps running the symporter until Na⁺ leaking in has run it down.

• 2.A gated Na⁺ channel opens in a resting cell. Which way does Na⁺ move, and why? Does this use ATP?Show answerHide

  Na⁺ rushes into the cell. Both parts of its electrochemical gradient point inward: Na⁺ is more concentrated outside, and the negative interior attracts positive ions. It's facilitated diffusion, so it uses no ATP (though the pump will later spend ATP restoring the gradient).

• 3.The rate of uptake of an amino acid rises with concentration and then plateaus. The cells can concentrate it to ten times the outside level, but only when Na⁺ is present outside. Classify the transport.Show answerHide

  It uses a carrier (the plateau shows saturation) and it moves the amino acid against its gradient, so it's active. The dependence on outside Na⁺ shows it's secondary active transport, a Na⁺–amino acid symport.