While hydrophobic molecules pass into and out of cells freely, biological membranes pose a significant barrier to the movement of hydrophilic molecules.

To overcome this barrier ions and other hydrophilic molecules, such as sugars and amino acids, pass through membranes in association with carriers, pores, channels and pumps.

• Carriers shuttle back and forth across the membrane with their "cargo". Hydrophilic molecules are picked up on one side of the membrane and released on the other. Each carrier is specific for a certain type of hydrophilic molecule

• Pores & channels sit within the membrane. They contain an aqueous channel as an integral part of their structure. Hydrophilic molecules of the right size and shape can pass through this channel. In many cases, whether a channel is open or closed can be regulated.

• Pumps use energy to actively move hydrophilic molecules across the membrane, often against a concentration gradient.

A number antibiotics are ion carriers, known as ionophores. They are made by one organism in order to suppress or regulate the growth of others.

The valinomycin-K⁺ complex is soluble within the hydrophobic core of the lipid membrane.

Once it enters the membrane, it diffuses across and can release the bound K⁺ ion on the other side. In the presence of valinomycin, the membrane becomes permeable to K⁺.

Gramicidin, made by the soil bacterium Bacillus brevis, is typical of a second class of ionophore antibiotic.

The functional gramicidin molecule is a dimer, a molecule composed of two subunits that combine to form a cylindrical structure with a hollow center.

The outer surface of the gramicidin dimer is hydrophobic and sits within the hydrophobic center of the membrane.

The molecule has a hydrophilic central pore. The shape of this pore determines which molecules can pass through the channel and which cannot.

While a carrier moves back and forth through the membrane, a channel remains stationary and the cargo moves through it.

Typically, channels can move many more molecules per unit time across the membrane than can a carrier.

There are number of different types of channels in the membranes of cells.

One perhaps surprising group are the aquaporins.

These and related proteins act as water channels. They increase the permeability of the membrane to water and other small hydrophilic molecules.

an aquaporin

Coupling gradients

Whether or not there will be a net movement of a molecule across a membrane depends upon a number of factors.

Perhaps the most basic determinant is the relative concentrations of the molecule on the two sides of the membrane. Assuming that the molecule we are interested in can move through the membrane.

If [molecule]_outside = [molecule]_inside, there will be no net movement of molecules across the membrane.

The system is in equilibrium, meaning that there is no net change over time. This does not mean that the system is static, molecules are still moving back and forth through the membrane, but there is no net flux.

If [molecule]_outside is not equal [molecule]_inside there is, by definition, a concentration gradient across the membrane.

If the molecule can pass through the membrane, there will be a net flux of molecules from the region of high concentration to the region of lower concentration.

This flux is driven by the energy stored in the concentration gradient.

Without added energy, there can be no net flux of molecules against their concentration gradient, that is from a region of low to high concentration.

So you might reasonably conclude that carriers and pores are unable to move molecules against their concentration gradients.

This is true of carriers and pores that move only a single type of molecule, which are known as uniporters.

But, there are more complex transporters. These are it known as coupled or co-transporters.

Coupled transporters come in two 'flavors', symporters and antiporters.

They transport different types of molecules.

Symporters transport these molecules together in the same direction.

Antiporters transport them in opposite directions.

Basically, the concentration gradient in one molecule acts as a battery to drive the movement of the other.

If there was no membrane or if the membrane were completely and freely permeable, this battery would run down very fast.

Pumping up gradients

If the membrane were completely impremeable to the molecules, the concentration gradient would remain forever, but the energy stored in it could not be used.

Because the membrane is semi-permeable, it can be used both to store and access energy.

Without the constant addition of energy, the energy stored in concentration gradients across the membrane disappates.

[molecule]_outside becomes equal to [molecule]_inside.

Generating a concentration gradient requires the expenditure of energy.

Molecules that directly use chemical energy to generate or maintain concentration gradients are known as pumps. These are complex protein machines.

There are a number of molecules that cells use to store and transfer chemical energy. The most important is adenosine triphosphate or ATP.

To release the energy stored in ATP the bond between the terminal or (gamma) phosphate group is broken.

This hydrolysis reaction releases a phosphate group (P_i), adenosine diphosphate (ADP) and energy.

When the -phosphate bond of ATP is broken, the energy release must be captured or it will be lost as heat.

In fact, some organisms keep themselves warm by "wasting" energy.

This leads to a change in the structure of the protein. The captured energy is released when the pump protein 'relaxes' back to its original structure.

In a pump protein, the cycle of energy driven changes in protein structure is tightly coupled to the process of moving molecules across the membrane.