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 various types of molecules, most of which are proteins. 

Never fear, we will discuss the basics of proteins later in the course!

• Carrier molecules 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 or class of molecule.

• Channel proteins 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; they can be turned on and off.

• Pump proteins use energy to actively move various types of molecules across the membrane, often against a concentration gradient.

Aquaporins and their relatives:  Typically, the size of molecules that a channel protein can transport involves the shape and charges associated with the channel within it. 

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

One perhaps surprising group of proteins 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.

In fact, in the absence of aquaporins, the rate of osmotic movement of water is dramatically reduced.

At the same time, aquaporins appear to be present in all organisms and to play a critical physiological role. 

• Which would you think would transport molecules across a membrane faster, a carrier, a channel, or a pump, and why?
• When would a carrier protein release a bound (hydrophobic) molecule?
• Why does an aquaporin channel not allow a Na+ ion to pass through it?  
• In considering the evolution of wall-less organisms, how might the expression of aquaporins be important?

As temperature increases, the membrane melts. The lipid tails become increasingly disordered.

Membrane fluidity is critical for the correct functioning of many membrane proteins. 

Cells control membrane fluidity by regulating the lipid composition of the membrane.  In particular, lipids can have hydrocarbon chains that are saturated or unsaturated.

In saturated hydrocarbon chains, the carbons are linked by single bonds. The hydrocarbon chain is flexible, but more or less straight.

In unsaturated hydrocarbon chains, some of the carbons are linked by double-bonds.

When a lipid is dehydrogenated, hydrogens are removed and –C=C– bonds are formed.

The presence of a –C=C– bond leads to a kink in the hydrocarbon chain.  Kinked chains cannot pack together as regularly as can straight (saturated) hydrocarbon chains.

Compare the saturated fatty acid stearic acid to the unsaturated fatty acid oleic acid. Both have the same number of carbons in their hydrocarbon chains.

While stearic acid melts at 69°C oleic acid melts at 13°C.

• Why do membrane lipids solidify at low temperature? How are van der Waals interactions involved?   Are H-bonds involved?
• Why does the presence of unsaturated bonds in the lipid chain alter the temperature at which the membrane solidifies?
• Predict the effect of changing the position of a double bond in a hydrocarbon chain on the temperature of solidification?
• Would a membrane be more permeable to small molecules at high or low temperature and why?  

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

First, the molecule must be able to pass through the membrane - the membrane must be permeable to it.

Second, the concentration of the molecule on one side of the membrane must be higher than the concentration on the other; such a difference in concentration between two places is known as a concentration gradient.  [There is, of course, an exception when energy using pumps is involved, which we will discuss below].

If [molecule]_outside equals [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 and no energy is used by the system.  This does not mean that the system is static, however, molecules are moving back and forth through the membrane, but there is no net flux.

If [molecule]_outside is not equal to [molecule]_inside there will be a net flux of molecules from the region of higher concentration to the region of lower concentration.  This flux is driven by the energy stored in the concentration gradient.

Our initial analysis of net flux assumes that there are proteins present that act as channels. 

However, there exist more complex transporters, known as co-transporters. Co-transporters come in two "flavors", symporters and antiporters.  Both transport two different types of molecules through a linked mechanism.

Symporters transport two molecules together in the same direction.  Examples are the Na⁺/galactose and Na⁺/I⁺ symporters

Antiporters, such as the GlpT glycerol-phosphate/phosphate transporter moves molecules (glycerol phosphate and phosphate) in opposite directions.

Using symporters or antiporters, it is possible to couple different concentration gradients, so that the flux of one type of molecule down its concentration gradient can be used to move another type of molecule up its concentration gradient.

Basically, a concentration gradient of one molecule acts as a source of energy (a battery) to drive the movement of the other.

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

• Assume that there exists a concentration gradient between two points.   Graph how the concentration changes as you move from one point to the other. 
• Now, what happens if there is an impermeable membrane between those two points; graph how the concentrations change under those conditions.  
• [A]_outside= 0.5M and [A]_inside = 0.1 M; in which direction will A move?   If there is no net flux of A, even if there is a concentration gradient between two points, what can we conclude?
• What does it mean to move up a concentration gradient?  Are there net fluxes of molecules that can move up their concentration gradients spontaneously?
• What happens to the movement of molecules through channels and transporters if we reverse the concentration gradients across the membrane?

Pumping up gradients:  If a membrane were completely impermeable, the concentration gradients across the membrane would remain stable.  On the other hand, it would not be possible for the cell to use the energy stored in these concentration gradients. 

Real biological membranes are semi-permeable; they can be used both to store and access energy.  The movement of different molecules across them differ, due to which transport proteins are present and active.

Because they are semi-permeable, biological membranes leak – without the constant addition of energy, the energy stored in concentration gradients across a membrane will dissipate over time, that is

[molecule]_outside will becomes equal to [molecule]_inside over time.

Generating and maintaining concentration gradients requires the expenditure of energy.

Molecules that directly use energy to generate or maintain concentration gradients are known as pumps.  These are complex protein machines – some can capture energy directly from light, others use chemical energy.

There are a number of molecules used to store and transfer chemical energy in biological systems.

Perhaps the most important is adenosine triphosphate or ATP.

To release the energy stored in ATP, the bond between the terminal or γ (gamma) phosphate group is broken and a new, higher energy (more stable) bond, is formed.

The difference between the two bond energies is available to do work.

Some, but not all of this energy is used to alter the structure of the pump protein, which leads to a change in protein structure and the pumping of molecules across the membrane (A_in to A_out). 

The cycle of energy-driven changes in protein structure is coupled to the process of moving molecules across the membrane.  Some of this energy is released when the pump protein "relaxes" back to its original structure.

Energy that is not captured will be lost as heat.  In fact, some organisms keep themselves warm by "wasting" energy, they hydrolyze ATP (ATP + H₂O to ADP + Pi) without using the energy released.

• What makes a biological membrane semi-permeable?
• Why do we need to add energy to maintain gradients?
• Why might an organism want to "waste" energy?
• Would it be possible to capture all of the energy associated with ATP hydrolysis?  What "law" gets in the way?