# 6.4: Transport to and across the membrane

So the question is, how does the membrane “decide” which molecules to allow into and out of the cell. If we think about it, there are three possible general mechanisms (let us know if you can think of more). Molecules can move on their own through the membrane, they can move passively across the membrane using some type of specific “carrier” or “channel”, or they could be moved actively using some kind of “pump”. Which types of carriers, channels, and pumps are present will determine what types of molecules move through the cell’s membrane. As you might deduce pumps require a source of energy to drive them. As we will see, in the vast majority of cases, these carriers, channels, and pumps are protein-based molecular machines, the structure of which we will consider in detail later on. We can think of this molecular movement reaction generically as:

$\text{Molecule}_{\text{outside}} \rightleftharpoons \text{Molecule}_{\text{inside membrane}} \rightleftharpoons \text{Molecule}_{\text{inside cell}}$

As with standard chemical reactions, movement through a membrane involves an activation energy, which amounts to the energy needed to pass through the membrane. So, you might well ask, why does the membrane, particularly the hydrophobic center of the membrane, pose a barrier to the movement of hydrophilic molecules. Here the answer involves the difference in the free energy of the moving molecule within an aqueous solution, including the hydrophilic surface region of the membrane, where H-bond type electrostatic interactions are common between molecules, and the hydrophobic region of the membrane, where only van der Waals interactions are present. The situation is exacerbated for charged molecules, since water molecules are typically organized in a dynamic shell around each ion. Instead of reactants and products we can plot the position of the molecule relative to the membrane. We are considering molecules of one particular substance moving through the membrane and so the identity of the molecule does not change during the transport reaction. If the concentrations of the molecules are the same on both sides of the membrane, then their Gibbs free energies are also equal, the system will be in equilibrium with respect to this reaction. In this case, as in the case of chemical reactions, there will be no net flux of the molecule across the membrane, but molecules will be moving back and forth across the membrane at an equal rate. The rate at which they move back and forth will depend on the size of the activation energy associated with moving across the membrane as well as the concentrations of the molecules.

If a molecule is hydrophobic (non-polar) it will be more soluble in the hydrophobic environment that exists in the central region of the membrane than it is in an aqueous environment. In contrast the situation will be distinctly different for hydrophilic molecules. By this point, we hope you will recognize that in a simple lipid-only membrane (a biologically unrealistic case), the shape of this graph, and specifically the height of the activation energy peak will vary depending upon the characteristics of the molecule we are considering moving as well as the membrane itself. If the molecule is large and highly hydrophilic, for example, if it is charged, the activation energy associated with crossing the membrane will be higher than if the molecule is small and uncharged. Just for fun, you might consider what the reaction diagram for a single lipid molecule might look like; where might it be located, and what energy barriers are associated with its movement (flipping) across a membrane. You can start by drawing the steps involved in "flipping" a lipid molecule's orientation with a membrane.

Let us begin with water itself, which is small and uncharged. When a water molecule begins to leave the aqueous phase and enter the hydrophobic (central) region of the membrane, there are no H-bonds to take the place of those that are lost, no strong molecular handshakes; the result is that often the molecule is “pulled back” into the water phase. Nevertheless, there are so many molecules of water outside (and inside) the cell, and water molecules are so small, that once they enter the membrane, they can pass through it. The activation energy for the Wateroutside⇌Waterinside reaction is low enough that water can pass through a membrane (in both directions) at a reasonable rate.

Small non-polar molecules, such as O2 and CO2, can (very much like water) pass through a biological membrane relatively easily. There is more than enough energy available through collisions with other molecules (thermal motion) to provide them with the energy needed to overcome the activation energy involved in passing through the membrane. However now we begin to see changes in the free energies of the molecules on the inside and outside of the cell. For example, in organisms that depend upon O2 (obligate aerobes), the O2 outside of the cell comes from the air; it is ultimately generated by plants that release O2 as a waste product. Once O2 enters the cell, it takes part in the reactions of respiration (we will get back to both processes further on.) The result is that the concentration of O2 outside the cell will be greater than the concentration of O2 inside the cell. That means that the free energy of O2 outside will be greater than the free energy of O2 inside. The reaction O2 outside⇌O2 inside is now thermodynamically favorable and there will be a net flux of O2 into the cell. We can consider how a similar situation applies to water. The intracellular domain of a cell is a concentrated solution of proteins and other molecules. Typically, the concentration of water outside of the cell is greater than the concentration of water inside the cell. Our first order presumption is that the reaction:

$H_2O_{outside} \rightleftharpoons H_2O_{inside}$

is favorable, so water will flow into a cell. So the obvious question is, what happens over time? We will return to how cell’s (and organisms) resolve this important problem shortly.

A video simulation of a water molecule moving through a membrane: http://youtu.be/ePGqRaQiBfc

## Contributors

• Michael W. Klymkowsky (University of Colorado Boulder) and Melanie M. Cooper (Michigan State University) with significant contributions by Emina Begovic & some editorial assistance of Rebecca Klymkowsky.