The cell membrane or plasma membrane has many functions, but the most basic one is to define the cell’s borders and keep the cell functional. The plasma membrane is selectively permeable. This means that the membrane allows some materials to freely enter or leave the cell, while other materials cannot move freely, but require a specialized structure, and occasionally, even energy investment for crossing.
Components and structure
A cell’s plasma membrane defines the cell, outlines its borders, and determines the nature of its interaction with its environment. Cells exclude some substances, take in others, and excrete still others, all in controlled quantities. The plasma membrane must be very flexible to allow certain cells, such as red and white blood cells, to change shape as they pass through narrow capillaries. These are the more obvious plasma membrane functions. In addition, the plasma membrane’s surface carries markers that allow cells to recognize one another, which is vital for tissue and organ formation during early development, and which later plays a role in the immune response’s “self” versus “non-self” distinction.
Among the most sophisticated plasma membrane functions is the ability for complex, integral proteins, receptors to transmit signals. These proteins act both as extracellular input receivers and as intracellular processing activators. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors, and they activate intracellular response cascades when their effectors are bound. Occasionally, viruses hijack receptors (HIV, human immunodeficiency virus, is one example) that use them to gain entry into cells, and at times, the genes encoding receptors become mutated, causing the signal transduction process to malfunction with disastrous consequences.
Fluid mosaic model
In the 1950s, transmission electron microscopy allowed researchers to see that the plasma membrane’s core consisted of a double, rather than a single, layer. In 1972, S.J. Singer and Garth L. Nicolson proposed a model that explains plasma membrane function better than the previous models. The explanation, the fluid mosaic model, has evolved somewhat over time, but it still best accounts for plasma membrane structure and function as we understand them nowadays.
The fluid mosaic model describes the plasma membrane structure as a mosaic of components – including phospholipids, cholesterol, proteins, and carbohydrates – that gives the membrane a fluid character. Plasma membranes range from 5 to 10 nm in thickness. For comparison, human red blood cells, visible via light microscopy, are approximately 8 μm wide, or approximately 1,000 times wider than a plasma membrane.
The plasma membrane looks a bit like a sandwich (Figure 3.1). In a nutshell, it is composed of a bilayer of phospholipids, with their hydrophobic, fatty acid tails in contact with each other. The landscape of the membrane is studded with proteins, some of which span the membrane. Some of these proteins serve to transport materials into or out of the cell. Carbohydrates are attached to some of the proteins and lipids on the outward-facing surface of the membrane. These form complexes that function to identify the cell to other cells.
Figure 3.1: The plasma membrane fluid mosaic model describes the plasma membrane as a fluid combination of phospholipids, cholesterol, and proteins. Carbohydrates attached to lipids (glycolipids) and to proteins (glycoproteins) extend from the membrane’s outward-facing surface. The plasma membrane’s exterior surface is not identical to its interior surface.
A plasma membrane’s principal components are: lipids (phospholipids and cholesterol), proteins, and carbohydrates attached to some of the lipids and proteins. A phospholipid is a molecule consisting of glycerol, two fatty acids, and a phosphate-linked head group. Cholesterol, another lipid comprised of four fused carbon rings, is situated alongside the phospholipids in the membrane’s core. Carbohydrates are present only on the plasma membrane’s exterior surface and are attached either to proteins, forming glycoproteins, or to lipids, forming glycolipids. Table 3.1 presents a summary of these components.
The protein, lipid, and carbohydrate proportions in the plasma membrane vary with cell type, but for a typical human cell, protein accounts for about 50 percent of the composition by mass, lipids (of all types) account for about 40 percent, and carbohydrates comprise the remaining 10 percent. However, protein and lipid concentration varies with different cell membranes. For example, myelin, an outgrowth of specialized cells’ membrane that insulates the peripheral nerves’ axons, contains only 18 percent protein and 76 percent lipid. The mitochondrial inner membrane contains 76 percent protein and only 24 percent lipid. The plasma membrane of human red blood cells is 30 percent lipid.
| Component | Location |
|---|---|
| Phospholipid | Main membrane fabric |
| Cholesterol | Attached between phospholipids and between the two phospholipid layers |
| Integral proteins (like integrins) | Embedded within the phospholipid layer(s); may or may not penetrate through both layers |
| Peripheral proteins | On the phospholipid bilayer’s inner or outer surface; not embedded within the phospholipids |
| Carbohydrates (components of glycoproteins and glycolipids) | Generally attached to proteins on the outside membrane layer |
Table 3.1: Plasma membrane components and functions.
Membrane fluidity
The membrane’s mosaic characteristic helps to illustrate its nature. The integral proteins and lipids exist in the membrane as separate but loosely attached molecules. These resemble the separate, multicolored tiles of a mosaic picture, and they float, moving somewhat with respect to one another. However, the membrane is not like a balloon that can expand and contract; rather, it is fairly rigid and can burst if penetrated or if a cell takes in too much water. Still, because of its mosaic nature, a very fine needle can easily penetrate a plasma membrane without causing it to burst, and the membrane will flow and self-seal when one extracts the needle. The membrane’s mosaic characteristics explain some but not all of its fluidity. There are two other factors that help maintain this fluid characteristic.
One factor is the nature of the phospholipids themselves. In their saturated form, the fatty acids in phospholipid tails are saturated with bound hydrogen atoms. There are no double bonds between adjacent carbon atoms. This results in tails that are relatively straight. In contrast, unsaturated fatty acids do not contain a maximal number of hydrogen atoms, but they do contain some double bonds between adjacent carbon atoms. A double bond results in a bend in the carbon string of approximately 30 degrees.
Another factor is the temperature. Thus, if decreasing temperatures compress saturated fatty acids with their straight tails, they press in on each other, making a dense and fairly rigid membrane. If unsaturated fatty acids are compressed, the “kinks” in their tails elbow adjacent phospholipid molecules away, maintaining some space between the phospholipid molecules. This “elbow room” helps to maintain fluidity in the membrane at temperatures at which membranes with saturated fatty acid tails in their phospholipids would “freeze” or solidify. The membrane’s relative fluidity is particularly important in a cold environment. A cold environment usually compresses membranes comprised largely of saturated fatty acids, making them less fluid and more susceptible to rupturing. Many organisms (fish are one example) are capable of adapting to cold environments by changing the proportion of unsaturated fatty acids in their membranes in response to lower temperature.
Animals have an additional membrane constituent that assists in maintaining fluidity. Cholesterol, which lies alongside the phospholipids in the membrane, tends to dampen temperature effects on the membrane. Thus, cholesterol functions as a buffer, preventing lower temperatures from inhibiting fluidity and preventing increased temperatures from increasing fluidity too much. Thus, this lipid extends, in both directions, the temperature range in which the membrane is appropriately fluid and, consequently, functional. Cholesterol also serves other functions, such as organizing clusters of transmembrane proteins into lipid rafts.
Plasma membrane transport
The best known role of the plasma membrane is transport. As the boundary between the intracellular and extracellular environment, plasma membranes must allow certain substances to enter and leave a cell, and prevent some harmful materials from entering and some essential materials from leaving. In other words, plasma membranes are selectively permeable – they allow some substances to pass through, but not others. If they were to lose this selectivity, the cell would no longer be able to sustain itself, and it would be destroyed.
Some cells require larger amounts of specific substances. They must have a way of obtaining these materials from extracellular fluids. This may happen passively, as certain materials move back and forth, or the cell may have special mechanisms that facilitate transport. Some materials are so important to a cell that it spends some of its energy, hydrolyzing adenosine triphosphate (ATP), to obtain these materials. Red blood cells use some of their energy doing just that. Most cells spend the majority of their energy to maintain an imbalance of sodium and potassium ions between the cell’s interior and exterior, as well as on protein synthesis.
Thus, there are two methods of membrane transport: pasive, which does not require energy, and active, which requires energy. To power the majority of energy-requiring cellular reactions. including transport, a cell uses the energy-supplying molecule ATP. Table 3.2 presents a summary of transport processes.
| Transport method | Active / Passive | Material transported |
|---|---|---|
| Diffusion | Passive | Small-molecular weight material |
| Osmosis | Passive | Water |
| Facilitated transport / diffusion | Passive | Sodium, potassium, calcium, glucose |
| Primary active transport | Active | Sodium, potassium, calcium |
| Secondary active transport | Active | Amino acids, lactose |
| Phagocytosis | Active | Large macromolecules, whole cells, or cellular structures |
| Pinocytosis and potocytosis | Active | Small molecules (liquids/water) |
| Receptor-mediated endocytosis | Active | Large quantities of macromolecules |
Table 3.2: Methods of transport, energy requirements, and types of transported material.
Passive transport
The most direct forms of membrane transport are passive. Passive transport is a naturally occurring phenomenon and does not require the cell to exert any of its energy to accomplish the movement. In passive transport, substances move from an area of higher concentration to an area of lower concentration. A physical space in which there is a single substance concentration range has a concentration gradient.
Selective permeability
Plasma membranes are asymmetric: the membrane’s interior is not identical to its exterior (Figure 3.1). There is a considerable difference between the array of phospholipids and proteins between the two leaflets that form a membrane. On the membrane’s interior, some proteins serve to anchor the membrane to cytoskeleton‘s fibers. There are peripheral proteins on the membrane’s exterior that bind extracellular matrix elements. Carbohydrates, attached to lipids or proteins, are also on the plasma membrane’s exterior surface. These carbohydrate complexes help the cell bind required substances in the extracellular fluid. This adds considerably to plasma membrane’s selective nature.
Recall that plasma membranes are amphiphilic: they have hydrophilic and hydrophobic regions. This characteristic helps move some materials through the membrane and hinders the movement of others. Non-polar and lipid-soluble material with a low molecular weight can easily slip through the membrane’s hydrophobic lipid core. Substances such as the fat-soluble vitamins A, D, E, and K readily pass through the plasma membranes in the digestive tract and other tissues. Fat-soluble drugs and hormones also gain easy entry into cells and readily transport themselves into the body’s tissues and organs. Oxygen and carbon dioxide molecules have no charge and pass through membranes by simple diffusion.
Polar substances present problems for the membrane. While some polar molecules connect easily with the cell’s outside, they cannot readily pass through the plasma membrane’s lipid core. Additionally, while small ions could easily slip through the spaces in the membrane’s mosaic, their charge prevents them from doing so. Ions such as sodium, potassium, calcium, and chloride must have special means of penetrating plasma membranes. Simple sugars and amino acids also need the help of various transmembrane proteins (channels) to transport themselves across plasma membranes.
Diffusion
Diffusion is a passive process of transport. A single substance moves from a high concentration to a low concentration area until the concentration is equal across a space. We are familiar with diffusion of substances through the air. For example, think about someone opening a bottle of ammonia in a room filled with people. The ammonia gas is at its highest concentration in the bottle. Its lowest concentration is at the room’s edges. The ammonia vapor will diffuse, or spread away, from the bottle, and gradually, increasingly more people will smell the ammonia as it spreads.
Materials move within the cell’s cytosol by diffusion, and certain materials move through the plasma membrane by diffusion. Diffusion expends no energy. On the contrary, concentration gradients are a form of potential energy, which dissipates as the gradient is eliminated. Each separate substance in a medium, such as the extracellular fluid, has its own concentration gradient, independent of other materials’ concentration gradients. In addition, each substance will diffuse according to that gradient. Within a system, there will be different diffusion rates of various substances in the medium.
Osmosis
Osmosis is a special case of diffusion. Water, like other substances, moves from an area of high concentration to one of low concentration. Osmosis is the movement of water through a semipermeable membrane according to the water’s concentration gradient across the membrane, which is inversely proportional to the solutes’ concentration. While diffusion transports material across membranes and within cells, osmosis transports only water across a membrane and the membrane limits the solutes’ diffusion in the water. Not surprisingly, the aquaporins that facilitate water movement play a large role in osmosis, most prominently in red blood cells and the membranes of kidney tubules.
Active transport
Active transport mechanisms require the cell’s energy, usually in the form of ATP. If a substance must move into the cell against its concentration gradient – that is, if the substance’s concentration inside the cell is greater than its concentration in the extracellular fluid (and vice versa) – the cell must use energy to move the substance. Some active transport mechanisms move small-molecular weight materials, such as ions, through the membrane. Other mechanisms transport much larger molecules.
A simple concentration gradient is a substance’s differential concentrations across a space or a membrane. In living systems gradients are more complex. Because ions move into and out of cells and because cells contain proteins that do not move across the membrane and are mostly negatively charged, there is also an electrical gradient, a difference of charge, across the plasma membrane. The interior of living cells is electrically negative with respect to the extracellular fluid in which they are bathed, and at the same time, cells have higher concentrations of potassium (K+) and lower concentrations of sodium (Na+) than the extracellular fluid.
Thus, in a living cell, the concentration gradient of Na+ tends to drive it into the cell, and its electrical gradient (a positive ion) also drives it inward to the negatively charged interior. However, the situation is more complex for other elements such as potassium. The electrical gradient of K+, a positive ion, also drives it into the cell, but the concentration gradient of K+ drives K+ out of the cell (Figure 3.2). The combined concentration gradient and electrical charge that affects an ion is called its electrochemical gradient.
Figure 3.2: Electrochemical gradients arise from the combined effects of concentration gradients and electrical gradients. Structures labeled A represent proteins.
To move substances against a concentration or electrochemical gradient, the cell must use energy. This energy comes from ATP generated through the cell’s metabolism. Active transport mechanisms, or pumps, work against electrochemical gradients. Small substances constantly pass through plasma membranes. Active transport maintains concentrations of ions and other substances that living cells require in the face of these passive movements. A cell may spend much of its metabolic energy supply maintaining these processes. (A red blood cell uses most of its metabolic energy to maintain the imbalance between exterior and interior sodium and potassium levels that the cell requires.) Because active transport mechanisms depend on a cell’s metabolism for energy, they are sensitive to many metabolic poisons that interfere with the ATP supply.
Two mechanisms exist for transporting small-molecular weight material and small molecules. Primary active transport moves ions across a membrane and creates a difference in charge across that membrane, which is directly dependent on ATP. Secondary active transport does not directly require ATP; instead, it is the movement of material due to the electrochemical gradient established by primary active transport.
Bulk transport
In addition to moving small ions and molecules through the membrane, cells also need to remove and take in larger molecules and particles. Some cells are even capable of engulfing entire unicellular microorganisms. In order to uptake and release large particles, a cell needs energy. A large particle, however, cannot pass through the membrane, even with energy that the cell supplies.
Endocytosis
Endocytosis is a type of active transport that moves particles, such as large molecules, parts of cells, and even whole cells, into a cell. There are different endocytosis variations, but all share a common characteristic: the cell’s plasma membrane invaginates, forming a pocket around the target particle. The pocket pinches off, resulting in the particle containing itself in a newly created intracellular vesicle formed from the plasma membrane.
Phagocytosis
Phagocytosis (Figure 3.3 top left) (the condition of “cell eating”) is the process by which a cell takes in large particles, such as other cells or relatively large particles. For example, when microorganisms invade the human body, a type of white blood cell, a neutrophil, will remove the invaders through this process, surrounding and engulfing the microorganism, which the neutrophil then destroys.
In preparation for phagocytosis, a portion of the plasma membrane’s inward-facing surface becomes coated with the protein clathrin, which stabilizes this membrane’s section. The membrane’s coated portion then extends from the cell’s body and surrounds the particle, eventually enclosing it. Once the vesicle containing the particle is enclosed within the cell, the clathrin disengages from the membrane and the vesicle merges with a lysosome for breaking down the material in the newly formed compartment (endosome). When accessible nutrients from the vesicular contents’ degradation have been extracted, the newly formed endosome merges with the plasma membrane and releases its contents into the extracellular fluid. The endosomal membrane again becomes part of the plasma membrane.
Pinocytosis
A variation of endocytosis is pinocytosis (Figure 3.3 bottom left). This literally means “cell drinking”. It is a process that takes in molecules, including water, which the cell needs from the extracellular fluid. Pinocytosis results in a much smaller vesicle than does phagocytosis, and the vesicle does not need to merge with a lysosome.
A variation of pinocytosis is potocytosis. This process uses a coating protein, caveolin, on the plasma membrane’s cytoplasmic side, which performs a similar function to clathrin. The cavities in the plasma membrane that form the vacuoles have membrane receptors and lipid rafts in addition to caveolin. The vacuoles or vesicles formed in caveolae (singular caveola) are smaller than those in pinocytosis. Potocytosis brings small molecules into the cell and transports them through the cell for their release on the other side, a process called transcytosis.
Receptor-mediated endocytosis
A targeted variation of endocytosis employs receptor proteins in the plasma membrane that have a specific binding affinity for certain substances. In receptor-mediated endocytosis (Figure 3.3 top right), as in phagocytosis, clathrin attaches to the plasma membrane’s cytoplasmic side. If a compound’s uptake is dependent on receptor-mediated endocytosis and the process is ineffective, the material will not be removed from the tissue fluids or blood. Instead, it will stay in those fluids and increase in concentration.
The failure of receptor-mediated endocytosis causes some human diseases. For example, receptor mediated endocytosis removes low density lipoprotein or LDL (or “bad” cholesterol) from the blood. In the human genetic disease familial hypercholesterolemia, the LDL receptors are defective or missing entirely. People with this condition have life-threatening levels of cholesterol in their blood, because their cells cannot clear LDL particles.
Although receptor-mediated endocytosis is designed to bring specific substances that are normally in the extracellular fluid into the cell, other substances may gain entry into the cell at the same site. Flu viruses, diphtheria, and cholera toxin all have sites that cross-react with normal receptor-binding sites and gain entry into cells.
Exocytosis
The reverse process of moving material into a cell is the process of exocytosis (Figure 3.3 bottom right). Exocytosis is the opposite of the processes discussed above in that its purpose is to expel material from the cell into the extracellular fluid. Waste material is enveloped in a membrane and fuses with the plasma membrane’s interior. This fusion opens the membranous envelope on the cell’s exterior, and the waste material expels into the extracellular space. Examples of cells releasing molecules via exocytosis include extracellular matrix protein secretion and neurotransmitter secretion into the synaptic cleft by synaptic vesicles.
 |
 |
 |
 |
Figure 3.3: Bulk transport processes: (top left) phagocytosis; (bottom left) pinocytosis; (top right) receptor-mediated endocytosis; (bottom right) exocytosis (credit: modification of work by Mariana Ruiz Villareal).
References:
- Fowler, Samantha, et al. Concepts of Biology. OpenStax College, Rice University, 2013. Download for free at: https://openstax.org/details/books/concepts-biology.
- Clark, Mary, Jung Choi, and Matthew Douglas. Biology 2E. 2018. Access for free at https://openstax.org/details/books/biology-2e.