The purpose of this unit is to concentrate on how some molecules can cross cell membranes while others cannot (the selectively permeable or semi-permeable nature of the cell membrane). The study of how molecules move across cell membranes is known as membrane transport physiology. A scientist who studies membrane transport could be a physiologist, a biochemist, or a cell biologist.

The cell membrane itself has many functions including:

Even though one can see cell membranes with high magnification electron microscopy as two dark lines with a lighter space in between, the chemical components of cell membranes in place are too small to be seen. Thus, most of the information about the structure of cell membranes comes from breaking down the cell membrane into its component molecules and then hypothesizing the potential shape of those molecules in the membrane (from an understanding of their chemical natures). The scientific area of crystallography has made great advances in recent years in predicting 3-dimensional structures of various complex molecules once the 2-dimensional components (in order) are known. The current best model of a cell membrane is known as the fluid mosaic model. It is similar to icebergs (the proteins) suspended in a sea of water (the phospholipids or fats). Another analogy would be that the proteins are like the raisins in raisin bread (the phospholipids).

A phospholipid molecule is chemically made up of glycerol, a phosphate group, and 2 fatty acids. The end of the molecule that is glycerol and the phosphate group likes to dissolve in water (is polar like water). [By polar, we mean that individual water molecules have one end (pole) that is relatively attracted to molecules with positive charge and one end that is relatively attracted to molecules with negative charge.] The end of the phospholipid molecule that contains the fatty acids is nonpolar (does not like to dissolve in water). Molecules or portions of molecules that are polar and like to dissolve in water are called hydrophilic or water-loving. Molecules or portions of molecules that are nonpolar and do not like to dissolve in water are called hydrophobic or water-hating. When phospholipids (molecules with both a polar end and a nonpolar end) are dissolved in water, the polar ends (called the heads) line up together near water and the nonpolar ends (called the tails) line up together near each other to form a phospholipid bilayer (double layer). This phospholipid bilayer looks under the electron microscope like two dark lines (the heads) with a lighter space in between (the tails). The phospholipid bilayer is the core of the cell membrane with the heads on the sides of the membrane facing outside the cell and inside the cell (toward the cytoplasm) and the tails inside the cell membrane itself. This phospholipid core means that molecules that can easily dissolve in phospholipids (fat-soluble molecules) can easily cross cell membranes.

The proteins embedded in the phospholipid bilayer have their own special functions for moving molecules across cell membranes. Certain proteins move specific small fat insoluble molecules across cell membranes without the use of cell energy (by diffusion). Diffusion is the movement of molecules across cell membranes from a higher concentration of the molecules to a lower concentration of the molecules (similar to turning off the engine and letting your car coast downhill). For example, there are special proteins in cell membranes that are needed to allow sugars (glucose and some others) and some of the amino acids to diffuse across the cell membrane. These important nutrient molecules are broken down inside the cells via various chemical reactions and made into adenosine triphosphate (ATP) in the mitochondria. ATP is able to provide energy to the cell for other functions because the last phosphate group (of the three) is bound to the next to the last phosphate group with a high energy chemical bond. When this bond is broken, the energy in it is available to the cell to use for other purposes. There are also special proteins in cell membranes that are needed to allow salts (ions) to diffuse across the cell membrane. For example, ions (like sodium, chloride, potassium, and calcium) are involved in initiating and continuing the electrical currents (like the action potential) that are important for the function of various excitable cells like nerve and muscle cells.

Certain proteins can only move specific small fat insoluble molecules across cell membranes when cell energy is available. Proteins that require cell energy to move molecules are known as active transport proteins. Because active transport proteins have chemical energy available to them, they can move molecules across cell membranes from a lower concentration of those molecules to a higher concentration of those molecules (similar to using gasoline to drive your car uphill). For example, the sodium-potassium pumps actively transport sodium ions uphill out of the cell at the same time that they pump potassium ions uphill into the cell by directly using the energy from the high energy phosphate bond in ATP. For another example, certain proteins in some cells use the continuous removal of sodium ions from the cell by the sodium-potassium pumps to simultaneously move new sodium ions downhill into the cell and nutrient molecules or other ions uphill across the cell membrane. Thus, these proteins indirectly need the energy provided by ATP. In other words if the cell does not have or cannot make ATP (as in starvation or poisoning of the cell), these proteins will sooner or later stop moving molecules (there will be no active transport). A good analogy is that you would be unlikely to be able to start your car without gasoline (like the proteins that directly use ATP). However if you are already going 60 mph and run out of gasoline (like the proteins that indirectly use ATP), you will coast for a while before you stop.

Recently scientists discovered that even water molecules sometimes use special proteins to cross cell membranes. Water is a very small fat insoluble molecule that sometimes can sneak or squeeze between the phospholipid molecules in the bilayer to cross cell membranes. However certain cells need water to move faster and have additional special water proteins (known as water channels). Water crosses cell membranes both through the lipid bilayer and through the protein water channels downhill by diffusion. The movement of water molecules by diffusion from a higher concentration of water molecules to a lower concentration of water molecules is known as osmosis. [In order to determine where there are more water molecules, one needs to consider what is dissolved in the water. A concentrated solution has many salt or sugar or other molecules dissolved in it (and thus a lower concentration of water molecules). A dilute solution has fewer salt or sugar or other molecules dissolved in it (and thus a higher concentration of water molecules). Osmosis (diffusion of water) will occur across a selectively permeable cell membrane from the side of the dilute solution to the side of the concentrated solution.] Therefore, certain molecules needed by cells can only cross the cell membrane if the special proteins for those molecules are embedded in the phospholipid bilayer of that cell. Thus, both the number of these special proteins in the cell membrane and the speed at which these proteins can move molecules contribute to the selective permeability of that cell’s membrane.

How are carbohydrates associated with cell membranes?

For completeness, cell membranes also have carbohydrates (sugar chains) associated with them. These carbohydrate chains may be attached to some of the phospholipids or to some of the proteins in the cell membrane. They are always attached to the side of the cell membrane that faces outside the cell. They help to form either an additional physical barrier for molecules to cross the cell membrane or binding sites for molecules outside the cell to communicate with the inside of the cell. Because glyco- is a prefix that signifies carbohydrate, the complex of carbohydrate groups on the outside of the cell membrane is known as the glycocalyx (sweet husk).

The phospholipid bilayer acts like a wall of fat for the cell. This means that only those molecules that can dissolve in fat (are fat or lipid soluble) can enter and leave cells by going through the lipid bilayer portion of the cell membrane. Some molecules are more fat soluble than others. For example, ethanol (the alcohol found in beer and wine) is fat-soluble and moves relatively quickly through the phospholipid bilayer into and out of cells. [This is why a breath test after ingesting too much alcohol detects how much alcohol one has consumed. The ethanol quickly moves from the stomach directly into the bloodstream (and then to the upper airways of the lungs where it is exhaled). Most consumed food and liquids need to be processed and to enter the small intestine before they are absorbed into the bloodstream.] However, simple fat (like butter fat) is even more fat soluble than ethanol and would be expected to be absorbed even faster into the bloodstream (some even in the mouth).

The number and kinds of special transport proteins found in the cell membrane also contribute to the selectively permeable or semi-permeable nature of the membrane. NEWS FLASH! Scientists used to believe that there were rather generic pores in cell membranes (either holes in the phospholipid bilayer, special proteins that acted like holes, or a combination of the two). Thus, a representation of a cell membrane as being semi-permeable usually looked at the size of the "pores" in the membrane (what size molecule could squeeze through those holes). Scientists now believe that most fat insoluble molecules that can move across cell membranes must have their own special proteins to be able to cross. Thus, the experiments in this unit using baggies with pores of various sizes to simulate cell membranes are only indicating that the cell membrane acts like a selectively permeable membrane with a given pore size. Most cell membranes do not actually have non-selective "pores".

How do fat-soluble molecules cross the cell membrane?

Since a large percentage of the cell membrane is the lipid bilayer, essentially all of the fat or lipid soluble molecules that want to cross a cell membrane can go across rapidly. The more fat molecules there are, the more that will cross the cell membrane. However one of the ways that scientists learned that some molecules needed special proteins to cross the cell membrane is by studying various molecules to see when the number of those molecules (per unit time) moving across the membrane leveled off. This leveling off of transport is known as saturation (the transport using all special proteins for that molecule is saturated or full).

The two different kinds of special transport proteins in cell membranes are known as carriers or channels. Carrier proteins never form a direct connection between the inside and the outside of the cell. A good analogy for understanding the basic design behind carrier proteins is that they are like the Panama Canal. The Panama Canal has a gate on the Atlantic side and one on the Pacific side and a separate canal in between (in which the water level and ship can be raised or lowered). Thus, a ship crossing the canal from east to west will enter through the gate on the Atlantic side and then the gate will close. While the ship is traversing the canal from east to west (with both gates closed), the water level is adjusted by pumping water in or out of the canal. Then the ship reaches the west end of the canal and the water level there is now the same as the Pacific Ocean. The gate to the Pacific side will open and the ship will leave the canal. At no time during the passage are both of the gates open at the same time. Likewise, a molecule being transported via a carrier protein out of a cell, binds to its site on the protein as the site faces inside the cell, moves across the cell membrane inside the protein as the protein changes its conformation, and then is released by the protein outside the cell. Some carrier proteins require cell energy to be able to transport molecules. This would be active transport and would be like the pumps that are needed to raise or lower water levels in the Panama Canal. Some carrier proteins do not require cell energy to be able to transport molecules. An analogy for this passive transport process could be a small stream connecting two small lakes in a chain of lakes.

In order to understand the characteristics (used by scientists) that are unique to transport processes that are mediated by proteins in cell membranes, a good analogy for middle school students is the school bus analogy. Picture that the carrier proteins in the cell membrane are like a school bus that needs to take children from one end of town to the school (across town is like across the cell membrane). This particular school bus has some seats that only children with round butts can sit in and some seats that only children with square butts can sit in. Thus the number and kinds of seats on the bus give the bus selectivity (like the binding sites on the proteins can only bind and select for certain molecules). The bus is not allowed to take more children than its number of seats. If the bus has 40 seats and less than 40 children are going to ride the bus to school, then no matter how many children board the bus they will all be able to go to school. If 41 children need to ride the bus, then the bus is full and only 40 children will arrive at school on that bus. If 60 children need to ride the bus, then the bus is still full and only 40 children will arrive at school on that bus. The full bus (like the full binding sites on the special proteins in the cell membrane) demonstrates saturation (so full that no more children than 40 can ride the bus that day). Suppose that some boys have round butts and some square butts and some girls have round butts and some square butts. If 20 of the seats on the bus are for square butt children, then the first 20 square butt children (girls or boys) who get on the bus will be able to ride the bus. Thus similar shaped children will compete for the seats on the bus (like similar shaped molecules exhibit competition for the binding sites on the proteins). Scientists formerly used this analogy to explain the movement of molecules across cell membranes with the special proteins. However, this well-known "ferry boat analogy" is not now thought to be the best representation of how the membrane proteins actually work. Most membrane proteins do not shuttle molecules across the cell membrane (liking riding in the bus from one end of town to the other). Instead most membrane proteins are thought to change shape in the cell membrane as the molecules bind and unbind. This would be like having the bus pick up the children across the street from the school with only the front door open. Once the children have taken seats on the bus, the back door of the bus will now be able to open and they can exit the bus at the entrance to the school. This is similar to the conformational (or shape) change of a protein as the appropriate molecules bind and unbind to its binding sites. The conformational change interpretation of the school bus analogy is a good one for understanding the special proteins in the cell membrane that scientists call carriers.

The other special proteins in cell membranes are known as channels (like the water channels and various ion channels). Channel proteins have water-filled passageways that link the inside and the outside of the cell. Channel proteins are more like pores. They are special proteins that have pore-like openings in the middle of them to allow certain types of molecules to go through them. For example, water channels have very small openings so that only very small water molecules can go through. Ion channels discriminate among various types of ions by having different sized openings and different electrical charges around the openings. Channel proteins thus exhibit selectivity and competition due to the characteristics of the openings and the entrances and exits of the openings. In addition, channel proteins exhibit saturation because they can be so full of the water or ion molecules that molecules need to go single file through the opening. Thus in order for one molecule to enter the opening, a molecule at the exit will need to leave. Channel proteins also have regions of the molecule that act like gates that swing open and closed. Channels are generally classified by whether their gates are usually open or closed.

So when scientists discover that the movement of certain molecules across the cell membrane exhibits saturation, competition, and/or selectivity; then they know that those molecules are using special proteins to cross the cell membrane. Why do cells need both channels and carriers? Channel proteins generally allow more rapid transport across the membrane but are less selective about what they transport. Carrier proteins are slower but are better at discriminating between closely related molecules.

Cell membranes are also important cell organelles that serve as both a gateway and a barrier for the cell. Cell membranes are made up of a lipid bilayer (fats) with proteins interspersed and some carbohydrates attached to either the lipids or the proteins on the outside of the cell membrane. The lipid bilayer part easily allows fat-soluble molecules (known as hydrophobic or water-hating) to cross the cell membrane. Fat-insoluble molecules (known as hydrophilic or water-loving) need to have their own special proteins embedded in the cell membrane to be able to cross (permeate) the cell membrane. [Since red blood cells can only use glucose for energy, they need many special proteins for glucose transport across their cell membranes. In fact, individual red blood cells are known to have as many as 300,000 special proteins for the transport of glucose and as many as 250,000 special proteins for the transport of water into the red blood cell!] Most special proteins in cell membranes are very selective about which molecules they can/will transport. Thus, cell membranes act like they are selectively permeable due to both the lipid bilayer and how many and which special proteins are found in the cell's membrane. Different cells in a mammal's body have different kinds and proportions of special proteins. So all cells are selectively permeable but they all allow different molecules to enter or leave via their cell membranes. There is really no such thing as a "typical cell".