We are searching data for your request:
Upon completion, a link will appear to access the found materials.
It is often stated that small molecules or nonpolar molecules can diffuse through the plasma membrane because they can pass through the middle nonpolar bit, but why don't the polar sides block these nonpolar molecules. Estrogen is nonpolar and can diffuse across the membrane right? Why don't the polar heads of the phospholipids block it? Or look at H+. H+ can't diffuse across the membrane because it's charged (it's not like nonpolar molecule have a repulsive force against it, neutral objects don't repel charged ones as far as I am aware, I don't get why we say polar and nonpolar repel each other, as I understand they just stick to themselves better than each other). Regardless, H+ a small charged molecule would be able to get past the hydrophilic heads right? Estrogen wouldn't be. Where am I going wrong here? Thanks!
Polar and nonpolar molecules don't actually "repel", it's that polar molecules attract each other much more than nonpolar molecules attract anything. Therefore, to take a polar molecule from the (polar) water on one side of the membrane and bury it in the nonpolar region in the middle of the membrane is difficult because it means breaking its relatively strong interactions with the polar water molecules without forming new strong interactions to compensate.
In the case of a nonpolar molecule passing through the membrane, it is already in water when it approaches the membrane, and transferring it past the polar head groups isn't much "worse" (there's likely a slight effect of the often charged head groups attracting ions that bridge them to one another, but this would be small). The large effect of it being nonpolar, however, is to make it less unfavorable to move it into the middle layer of the membrane where there aren't polar groups for it to interact with.
Why doesn't the polar side of the plasma membrane block nonpolar diffusion? - Biology
Diffusion is a process of passive transport in which molecules move from an area of higher concentration to one of lower concentration.
Describe diffusion and the factors that affect how materials move across the cell membrane.
- Substances diffuse according to their concentration gradient within a system, different substances in the medium will each diffuse at different rates according to their individual gradients.
- After a substance has diffused completely through a space, removing its concentration gradient, molecules will still move around in the space, but there will be no net movement of the number of molecules from one area to another, a state known as dynamic equilibrium.
- Several factors affect the rate of diffusion of a solute including the mass of the solute, the temperature of the environment, the solvent density, and the distance traveled.
- diffusion: The passive movement of a solute across a permeable membrane
- concentration gradient: A concentration gradient is present when a membrane separates two different concentrations of molecules.
When someone is cooking food in a kitchen, the smell begins to waft through the house, and eventually everyone can tell what’s for dinner! This is due to the diffusion of odor molecules through the air, from an area of high concentration (the kitchen) to areas of low concentration (your upstairs bedroom).
Diffusion is a passive process of transport. A single substance tends to move from an area of high concentration to an area of low concentration until the concentration is equal across a space. You 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 edges of the room. The ammonia vapor will diffuse, or spread away, from the bottle gradually, more and 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, dissipated as the gradient is eliminated.
Diffusion: Diffusion through a permeable membrane moves a substance from an area of high concentration (extracellular fluid, in this case) down its concentration gradient (into the cytoplasm).
Each separate substance in a medium, such as the extracellular fluid, has its own concentration gradient independent of the concentration gradients of other materials. In addition, each substance will diffuse according to that gradient. Within a system, there will be different rates of diffusion of the different substances in the medium.
Factors That Affect Diffusion
Molecules move constantly in a random manner at a rate that depends on their mass, their environment, and the amount of thermal energy they possess, which in turn is a function of temperature. This movement accounts for the diffusion of molecules through whatever medium in which they are localized. A substance will tend to move into any space available to it until it is evenly distributed throughout it. After a substance has diffused completely through a space removing its concentration gradient, molecules will still move around in the space, but there will be no net movement of the number of molecules from one area to another. This lack of a concentration gradient in which there is no net movement of a substance is known as dynamic equilibrium. While diffusion will go forward in the presence of a concentration gradient of a substance, several factors affect the rate of diffusion:
- Extent of the concentration gradient: The greater the difference in concentration, the more rapid the diffusion. The closer the distribution of the material gets to equilibrium, the slower the rate of diffusion becomes.
- Mass of the molecules diffusing: Heavier molecules move more slowly therefore, they diffuse more slowly. The reverse is true for lighter molecules.
- Temperature: Higher temperatures increase the energy and therefore the movement of the molecules, increasing the rate of diffusion. Lower temperatures decrease the energy of the molecules, thus decreasing the rate of diffusion.
- Solvent density: As the density of a solvent increases, the rate of diffusion decreases. The molecules slow down because they have a more difficult time getting through the denser medium. If the medium is less dense, diffusion increases. Because cells primarily use diffusion to move materials within the cytoplasm, any increase in the cytoplasm’s density will inhibit the movement of the materials. An example of this is a person experiencing dehydration. As the body’s cells lose water, the rate of diffusion decreases in the cytoplasm, and the cells’ functions deteriorate. Neurons tend to be very sensitive to this effect. Dehydration frequently leads to unconsciousness and possibly coma because of the decrease in diffusion rate within the cells.
- Solubility: As discussed earlier, nonpolar or lipid-soluble materials pass through plasma membranes more easily than polar materials, allowing a faster rate of diffusion.
- Surface area and thickness of the plasma membrane: Increased surface area increases the rate of diffusion, whereas a thicker membrane reduces it.
- Distance travelled: The greater the distance that a substance must travel, the slower the rate of diffusion. This places an upper limitation on cell size. A large, spherical cell will die because nutrients or waste cannot reach or leave the center of the cell. Therefore, cells must either be small in size, as in the case of many prokaryotes, or be flattened, as with many single-celled eukaryotes.
A variation of diffusion is the process of filtration. In filtration, material moves according to its concentration gradient through a membrane sometimes the rate of diffusion is enhanced by pressure, causing the substances to filter more rapidly. This occurs in the kidney where blood pressure forces large amounts of water and accompanying dissolved substances, or solutes, out of the blood and into the renal tubules. The rate of diffusion in this instance is almost totally dependent on pressure. One of the effects of high blood pressure is the appearance of protein in the urine, which is “squeezed through” by the abnormally high pressure.
Atoms consist of an inner core called the nucleus and an outer shell that contains electrons. The most stable atoms, which happen to be the inert or noble gases, carry eight electrons in their outer shells. They do not attract other atoms, which means they are nonpolar, or electropositive. The other form of nonpolar atom is one that has only one electron in its outer shell. This means it is also nonpolar and electropositive. Nonpolar atoms do not mix with polar substances like water, so they are called hydrophobic atoms.
Membrane Proteins Can Be Associated with the Lipid Bilayer in Various Ways
Different membrane proteins are associated with the membranes in different ways, as illustrated in Figure 10-17. Many extend through the lipid bilayer, with part of their mass on either side (examples 1, 2, and 3 in Figure 10-17). Like their lipid neighbors, these transmembrane proteins are amphipathic, having regions that are hydrophobic and regions that are hydrophilic. Their hydrophobic regions pass through the membrane and interact with the hydrophobic tails of the lipid molecules in the interior of the bilayer, where they are sequestered away from water. Their hydrophilic regions are exposed to water on either side of the membrane. The hydrophobicity of some of these transmembrane proteins is increased by the covalent attachment of a fatty acid chain that inserts into the cytosolic monolayer of the lipid bilayer (example 1 in Figure 10-17).
Various ways in which membrane proteins associate with the lipid bilayer. Most trans-membrane proteins are thought to extend across the bilayer as (1) a single α helix, (2) as multiple α helices, or (3) as a rolled-up β sheet (a (more. )
Other membrane proteins are located entirely in the cytosol and are associated with the cytosolic monolayer of the lipid bilayer either by an amphipathic α helix exposed on the surface of the protein (example 4 in Figure 10-17) or by one or more covalently attached lipid chains, which can be fatty acid chains or prenyl groups (example 5 in Figure 10-17 and Figure 10-18). Yet other membrane proteins are entirely exposed at the external cell surface, being attached to the lipid bilayer only by a covalent linkage (via a specific oligosaccharide) to phosphatidylinositol in the outer lipid monolayer of the plasma membrane (example 6 in Figure 10-17).
Membrane protein attachment by a fatty acid chain or a prenyl group. The covalent attachment of either type of lipid can help localize a water-soluble protein to a membrane after its synthesis in the cytosol. (A) A fatty acid chain (myristic acid) is (more. )
The lipid-linked proteins in example 5 in Figure 10-17 are made as soluble proteins in the cytosol and are subsequently directed to the membrane by the covalent attachment of a lipid group (see Figure 10-18). The proteins in example 6, however, are made as single-pass transmembrane proteins in the ER. While still in the ER, the transmembrane segment of the protein is cleaved off and a glycosylphosphatidylinositol (GPI) anchor is added, leaving the protein bound to the noncytosolic surface of the membrane solely by this anchor (discussed in Chapter 12). Proteins bound to the plasma membrane by a GPI anchor can be readily distinguished by the use of an enzyme called phosphatidylinositol-specific phospholipase C. This enzyme cuts these proteins free from their anchors, thereby releasing them from the membrane.
Some membrane proteins do not extend into the hydrophobic interior of the lipid bilayer at all they are instead bound to either face of the membrane by noncovalent interactions with other membrane proteins (examples 7 and 8 in Figure 10-17). Many of the proteins of this type can be released from the membrane by relatively gentle extraction procedures, such as exposure to solutions of very high or low ionic strength or of extreme pH, which interfere with protein-protein interactions but leave the lipid bilayer intact these proteins are referred to as peripheral membrane proteins. Transmembrane proteins, many proteins held in the bilayer by lipid groups, and some proteins held on the membrane by unusually tight binding to other proteins cannot be released in these ways. These proteins are called integral membrane proteins.
How a membrane protein associates with the lipid bilayer reflects the function of the protein. Only transmembrane proteins can function on both sides of the bilayer or transport molecules across it. Cell-surface receptors are transmembrane proteins that bind signal molecules in the extracellular space and generate different intracellular signals on the opposite side of the plasma membrane. Proteins that function on only one side of the lipid bilayer, by contrast, are often associated exclusively with either the lipid monolayer or a protein domain on that side. Some of the proteins involved in intracellular signaling, for example, are bound to the cytosolic half of the plasma membrane by one or more covalently attached lipid groups.
In facilitated transport, also called facilitated diffusion, materials diffuse across the plasma membrane with the help of membrane proteins. A concentration gradient exists that would allow these materials to diffuse into the cell without expending cellular energy. However, these materials are ions or polar molecules that are repelled by the hydrophobic parts of the cell membrane. Facilitated transport proteins shield these materials from the repulsive force of the membrane, allowing them to diffuse into the cell.
The material being transported is first attached to protein or glycoprotein receptors on the exterior surface of the plasma membrane. This allows the material that is needed by the cell to be removed from the extracellular fluid. The substances are then passed to specific integral proteins that facilitate their passage. Some of these integral proteins are collections of beta pleated sheets that form a pore or channel through the phospholipid bilayer. Others are carrier proteins which bind with the substance and aid its diffusion through the membrane.
Figure 4. Facilitated transport moves substances down their concentration gradients. They may cross the plasma membrane with the aid of channel proteins. (credit: modification of work by Mariana Ruiz Villareal)
The integral proteins involved in facilitated transport are collectively referred to as transport proteins, and they function as either channels for the material or carriers. In both cases, they are transmembrane proteins. Channels are specific for the substance that is being transported. Channel proteins have hydrophilic domains exposed to the intracellular and extracellular fluids they additionally have a hydrophilic channel through their core that provides a hydrated opening through the membrane layers (Figure 4). Passage through the channel allows polar compounds to avoid the nonpolar central layer of the plasma membrane that would otherwise slow or prevent their entry into the cell. Aquaporins are channel proteins that allow water to pass through the membrane at a very high rate.
Channel proteins are either open at all times or they are “gated,” which controls the opening of the channel. The attachment of a particular ion to the channel protein may control the opening, or other mechanisms or substances may be involved. In some tissues, sodium and chloride ions pass freely through open channels, whereas in other tissues a gate must be opened to allow passage. An example of this occurs in the kidney, where both forms of channels are found in different parts of the renal tubules. Cells involved in the transmission of electrical impulses, such as nerve and muscle cells, have gated channels for sodium, potassium, and calcium in their membranes. Opening and closing of these channels changes the relative concentrations on opposing sides of the membrane of these ions, resulting in the facilitation of electrical transmission along membranes (in the case of nerve cells) or in muscle contraction (in the case of muscle cells).
Another type of protein embedded in the plasma membrane is a carrier protein. This aptly named protein binds a substance and, in doing so, triggers a change of its own shape, moving the bound molecule from the outside of the cell to its interior (Figure 5) depending on the gradient, the material may move in the opposite direction. Carrier proteins are typically specific for a single substance. This selectivity adds to the overall selectivity of the plasma membrane. The exact mechanism for the change of shape is poorly understood. Proteins can change shape when their hydrogen bonds are affected, but this may not fully explain this mechanism. Each carrier protein is specific to one substance, and there are a finite number of these proteins in any membrane. This can cause problems in transporting enough of the material for the cell to function properly. When all of the proteins are bound to their ligands, they are saturated and the rate of transport is at its maximum. Increasing the concentration gradient at this point will not result in an increased rate of transport.
Figure 5. Some substances are able to move down their concentration gradient across the plasma membrane with the aid of carrier proteins. Carrier proteins change shape as they move molecules across the membrane. (credit: modification of work by Mariana Ruiz Villareal)
An example of this process occurs in the kidney. Glucose, water, salts, ions, and amino acids needed by the body are filtered in one part of the kidney. This filtrate, which includes glucose, is then reabsorbed in another part of the kidney. Because there are only a finite number of carrier proteins for glucose, if more glucose is present than the proteins can handle, the excess is not transported and it is excreted from the body in the urine. In a diabetic individual, this is described as “spilling glucose into the urine.” A different group of carrier proteins called glucose transport proteins, or GLUTs, are involved in transporting glucose and other hexose sugars through plasma membranes within the body.
Channel and carrier proteins transport material at different rates. Channel proteins transport much more quickly than do carrier proteins. Channel proteins facilitate diffusion at a rate of tens of millions of molecules per second, whereas carrier proteins work at a rate of a thousand to a million molecules per second.
Why doesn't the polar side of the plasma membrane block nonpolar diffusion? - Biology
One of the great wonders of the cell membrane is its ability to regulate the concentration of substances inside the cell. These substances include ions such as Ca ++ , Na + , K + , and Cl – nutrients including sugars, fatty acids, and amino acids and waste products, particularly carbon dioxide (CO2), which must leave the cell. The membrane’s lipid bilayer structure provides the first level of control. The phospholipids are tightly packed together, and the membrane has a hydrophobic interior. This structure causes the membrane to be selectively permeable. A membrane that has selective permeability allows only substances meeting certain criteria to pass through it unaided. In the case of the cell membrane, only relatively small, nonpolar materials can move through the lipid bilayer (remember, the lipid tails of the membrane are nonpolar). Some examples of these are other lipids, oxygen and carbon dioxide gases, and alcohol. However, water-soluble materials—like glucose, amino acids, and electrolytes—need some assistance to cross the membrane because they are repelled by the hydrophobic tails of the phospholipid bilayer.
All substances that move through the membrane do so by one of two general methods, which are categorized based on whether or not energy is required. Passive transport is the movement of substances across the membrane without the expenditure of cellular energy. In contrast, active transport is the movement of substances across the membrane using energy from adenosine triphosphate (ATP).
In order to understand how substances move passively across a cell membrane, it is necessary to understand concentration gradients and diffusion. A concentration gradient is the difference in concentration of a substance across a space. Molecules (or ions) will spread/diffuse from where they are more concentrated to where they are less concentrated until they are equally distributed in that space. (When molecules move in this way, they are said to move down their concentration gradient.) Three common types of passive transport include simple diffusion, osmosis, and facilitated diffusion.
Simple Diffusion is the movement of particles from an area of higher concentration to an area of lower concentration. A couple of common examples will help to illustrate this concept. Imagine being inside a closed bathroom. If a bottle of perfume were sprayed, the scent molecules would naturally diffuse from the spot where they left the bottle to all corners of the bathroom, and this diffusion would go on until no more concentration gradient remains. Another example is a spoonful of sugar placed in a cup of tea. Eventually the sugar will diffuse throughout the tea until no concentration gradient remains. In both cases, if the room is warmer or the tea hotter, diffusion occurs even faster as the molecules are bumping into each other and spreading out faster than at cooler temperatures. Having an internal body temperature around 98.6 ° F thus also aids in diffusion of particles within the body.
Visit this link to see diffusion and how it is propelled by the kinetic energy of molecules in solution. How does temperature affect diffusion rate, and why?
Whenever a substance exists in greater concentration on one side of a semipermeable membrane, such as the plasma membrane, any substance that can move down its concentration gradient across the membrane will do so. Consider substances that can easily diffuse through the lipid bilayer of the cell membrane, such as the gases oxygen (O2) and CO2. O2 generally diffuses into cells because it is more concentrated outside of them, and CO2 typically diffuses out of cells because it is more concentrated inside of them. Neither of these examples requires any energy on the part of the cell, and therefore they use passive transport to move across the membrane. Before moving on, you need to review the gases that can diffuse across a cell membrane. Because cells rapidly use up oxygen during metabolism, there is typically a lower concentration of O2 inside the cell than outside. As a result, oxygen will diffuse from the interstitial fluid directly through the lipid bilayer of the membrane and into the cytoplasm within the cell. On the other hand, because cells produce CO2 as a byproduct of metabolism, CO2 concentrations rise within the cytoplasm therefore, CO2 will move from the cell through the lipid bilayer and into the interstitial fluid, where its concentration is lower. This mechanism of molecules spreading from where they are more concentrated to where they are less concentration is a form of passive transport called simple diffusion (Figure 3.15).
Osmosis is the diffusion of water through a semipermeable membrane (Figure 3.16). Water can move freely across the cell membrane of all cells, either through protein channels or by slipping between the lipid tails of the membrane itself. However, it is concentration of solutes within the water that determine whether or not water will be moving into the cell, out of the cell, or both.
Solutes within a solution create osmotic pressure , a pressure that pulls water. Osmosis occurs when there is an imbalance of solutes outside of a cell versus inside the cell. The more solute a solution contains, the greater the osmotic pressure that solution will have. A solution that has a higher concentration of solutes than another solution is said to be hypertonic. Water molecules tend to diffuse into a hypertonic solution because the higher osmotic pressure pulls water (Figure 3.17). If a cell is placed in a hypertonic solution, the cells will shrivel or crenate as water leaves the cell via osmosis. In contrast, a solution that has a lower concentration of solutes than another solution is said to be hypotonic. Cells in a hypotonic solution will take on too much water and swell, with the risk of eventually bursting, a process called lysis. A critical aspect of homeostasis in living things is to create an internal environment in which all of the body’s cells are in an isotonic solution, an environment in which two solutions have the same concentration of solutes (equal osmotic pressure). When cells and their extracellular environments are isotonic , the concentration of water molecules is the same outside and inside the cells, so water flows both in and out and the cells maintain their normal shape (and function). Various organ systems, particularly the kidneys, work to maintain this homeostasis.
Facilitated diffusion is the diffusion process used for those substances that cannot cross the lipid bilayer due to their size and/or polarity (Figure 3.18). A common example of facilitated diffusion is the movement of glucose into the cell, where it is used to make ATP. Although glucose can be more concentrated outside of a cell, it cannot cross the lipid bilayer via simple diffusion because it is both large and polar. To resolve this, a specialized carrier protein called the glucose transporter will transfer glucose molecules into the cell to facilitate its inward diffusion. There are many other solutes that must undergo facilitated diffusion to move into a cell, such as amino acids, or to move out of a cell, such as wastes. Because facilitated diffusion is a passive process, it does not require energy expenditure by the cell.
For all of the transport methods described above, the cell expends no energy. Membrane proteins that aid in the passive transport of substances do so without the use of ATP. During active transport, ATP is required to move a substance across a membrane, often with the help of protein carriers, and usually against its concentration gradient. One of the most common types of active transport involves proteins that serve as pumps. The word “pump” probably conjures up thoughts of using energy to pump up the tire of a bicycle or a basketball. Similarly, energy from ATP is required for these membrane proteins to transport substances—molecules or ions—across the membrane, usually against their concentration gradients (from an area of low concentration to an area of high concentration). The sodium-potassium pump , which is also called N + /K + ATPase, transports sodium out of a cell while moving potassium into the cell. The Na + /K + pump is an important ion pump found in the membranes of many types of cells. These pumps are particularly abundant in nerve cells, which are constantly pumping out sodium ions and pulling in potassium ions to maintain an electrical gradient across their cell membranes. An electrical gradient is a difference in electrical charge across a space. In the case of nerve cells, for example, the electrical gradient exists between the inside and outside of the cell, with the inside being negatively-charged (at around -70 mV) relative to the outside. The negative electrical gradient is maintained because each Na + /K + pump moves three Na + ions out of the cell and two K + ions into the cell for each ATP molecule that is used (Figure 3.19). This process is so important for nerve cells that it accounts for the majority of their ATP usage.
Other forms of active transport do not involve membrane carriers. Endocytosis (bringing “into the cell”) is the process of a cell ingesting material by enveloping it in a portion of its cell membrane, and then pinching off that portion of membrane (Figure 3.20). Once pinched off, the portion of membrane and its contents becomes an independent, intracellular vesicle. A vesicle is a membranous sac—a spherical and hollow organelle bounded by a lipid bilayer membrane. Endocytosis often brings materials into the cell that must to be broken down or digested. Phagocytosis (“cell eating”) is the endocytosis of large particles. Many immune cells engage in phagocytosis of invading pathogens. Like little Pac-men, their job is to patrol body tissues for unwanted matter, such as invading bacterial cells, phagocytize them, and digest them. In contrast to phagocytosis, pinocytosis (“cell drinking”) brings fluid containing dissolved substances into a cell through membrane vesicles. Phagocytosis and pinocytosis take in large portions of extracellular material, and they are typically not highly selective in the substances they bring in. Cells regulate the endocytosis of specific substances via receptor-mediated endocytosis.Receptor-mediated endocytosis is endocytosis by a portion of the cell membrane that contains many receptors that are specific for a certain substance. Once the surface receptors have bound sufficient amounts of the specific substance (the receptor’s ligand), the cell will endocytose the part of the cell membrane containing the receptor-ligand complexes. Iron, a required component of hemoglobin, is endocytosed by red blood cells in this way.
In contrast with endocytosis, exocytosis (taking “out of the cell”) is the process of a cell exporting material using vesicular transport (Figure 3.21). Many cells manufacture substances that must be secreted, like a factory manufacturing a product for export. These substances are typically packaged into membrane-bound vesicles within the cell. When the vesicle membrane fuses with the cell membrane, the vesicle releases it contents into the interstitial fluid. The vesicle membrane then becomes part of the cell membrane. Cells of the stomach and pancreas produce and secrete digestive enzymes through exocytosis (Figure 3.22). Endocrine cells produce and secrete hormones that are sent throughout the body, and certain immune cells produce and secrete large amounts of histamine, a chemical important for immune responses.
Why doesn't the polar side of the plasma membrane block nonpolar diffusion? - Biology
Review of Membrane Structure
- The plasma membrane plays a crucial role in the function of cells and in the life processes of organisms.
form a hydrophobic barrier at the the periphery.
- How do phospholipids react in an aqueous environment to form a bilayer membrane?
- Why are membrane proteins so important and how are they positioned within a membrane?
How Do Molecules Cross the Plasma Membrane?
- The plasma membrane is selectively permeable hydrophobic molecules and small polar molecules can diffuse through the lipid layer, but ions and large polar molecules cannot.
- Proteins which form channels may be utilized to enable the transport of water and other hydrophilic molecules these channels are often gated to regulate transport rate.
- The process of exocytosis expels large molecules from the cell and is used for cell secretion.
The plasma membrane has different types of proteins. Some are on the surface of this barrier, while others are embedded inside. Proteins can act as channels or receptors for the cell.
Integral membrane proteins are located inside the phospholipid bilayer. Most of them are transmembrane proteins, which means parts of them are visible on both sides of the bilayer because they stick out.
In general, integral proteins help transport larger molecules such as glucose. Other integral proteins act as channels for ions.
These proteins have polar and nonpolar regions similar to the ones found in phospholipids. On the other hand, peripheral proteins are located on the surface of the phospholipid bilayer. Sometimes they are attached to integral proteins.
4.3: Membrane Transport Proteins
- Contributed by E. V. Wong
- Axolotl Academica Publishing (Biology) at Axolotl Academica Publishing
Membrane proteins come in two basic types: integral membrane proteins (sometimes called intrinsic), which are directly inserted within the phospholipid bilayer, and peripheral membrane proteins (sometimes called extrinsic), which are located very close or even in contact with one face of the membrane, but do not extend into the hydrophobic core of the bilayer. Integral membrane proteins may extend completely through the membrane contacting both the extracellular environment and the cytoplasm, or they may only insert partially into the membrane (on either side) and contact only the cytoplasm or extracellular environment. There are no known proteins that are completely buried within the membrane core.
Integral membrane proteins (Figure (PageIndex<9>)) are held tightly in place by hydrophobic forces, and purification of them from the lipids requires membrane-disrupting agents such as organic solvents (e.g. methanol) or detergents (e.g. SDS, Triton X-100). Due to the nature of the bilayer, the portion of integral membrane proteins that lie within the hydrophobic core of the membrane are usually very hydrophobic in character, or have outward-facing hydrophobic residues to interact with the membrane core. These transmembrane domains usually take one of the two forms depicted in Figures 8 and 14: alpha helices - either individually or in a set with other alpha helices, or barrel-shaped insertions in which the barrel walls are constructed of beta-pleated sheets. The hydrophobic insertions are bounded by a short series of polar or charged residues that interact with the aqueous environment and polar head groups to prevent the hydrophobic portion of the protein from sliding out of place. Furthermore, proteins can have multiple membrane- spanning domains.
Figure (PageIndex<9>). Integral (orange) and peripheral (blue) membrane proteins embedded in a phospholipid bilayer.
Peripheral membrane proteins (also shown in Figure (PageIndex<9>)) are less predictable in their structure, but may be attached to the membrane either by interaction with integral membrane proteins or by covalently attached lipids. The most common such modifications to peripheral membrane proteins are fatty acylation, prenylation, and linkage to glycosylphosphatidylinositol (GPI) anchors. Fatty acylation is most often a myristoylation (a 14:0 acyl chain) and palmitoylation (a 16:0 chain) of the protein. A protein may be acylated with more than one chain, although one or two acyl groups is most common. These fatty acyl chains stably insert into the core of the phospholipid bilayer. While myristoylated proteins are found in a variety of compartments, almost all palmitoylated proteins are located on the cytoplasmic face of the plasma membrane. Prenylated proteins, on the other hand, are primarily found attached to intracellular membranes. Prenylation is the covalent attachment of isoprenoids to the protein - most commonly isoprene (a C5 hydrocarbon), farnesyl (C15), or geranylgeranyl (C20) groups (Figure (PageIndex<10>)). GPI anchors (Figure (PageIndex<11>)) are found exclusively on proteins on the outer surface of the cell, but there does not appear to be any other commonality in their structures or functions.
Figure (PageIndex<10>). Prenylation Figure (PageIndex<11>). GPI-linked proteins are connected by the C-terminal carboxyl group to phosphoethanolamine, which is linked to a core tetrasaccharide of three mannose residues and one N-acetylglucoasmine, the latter of which is bound by glycosidic linkage to a phosphatidylinositol.
Of course, not all membrane proteins, or even all transmembrane proteins, are transporters, and the many other functions of membrane proteins - as receptors, adhesion molecules, signaling molecules, and structural molecules - will be discussed in subsequent chapers. The focus here is on the role of membrane proteins in facilitating transport of molecules across the cell membrane.
Transport across the membrane may be either passive, requiring no external source of energy as solute travels from high to low concentration, or active, requiring energy expenditure as solute travels from low to high concentration (Figure (PageIndex<12>)).
Figure (PageIndex<12>). For Na ions and animal cells, passive transport is inward, sending Na+ from the high concentration outside the cell to the low concentration inside. Active transport requires energy such as ATP hydrolysis to push a Na + ion from the low concentration inside the cell to the higher concentration outside.
Passive transport can also be divided into nonmediated transport, in which the movement of solutes is determined solely by diffusion, and the solute does not require a transport protein, and mediated passive transport (aka facilitated diffusion) in which a transport protein is required to help a solute go from high to low concentration. Even though this may sometimes involve a change in conformation, no external energy is required for this process. Nonmediated passive transport applies only to membrane-soluble small nonpolar molecules, and the kinetics of the movement is ruled by diffusion, thickness of the membrane, and the electro-chemical membrane potential. Active transport is always a mediated transport process.
Figure (PageIndex<13>). Non-mediated and Mediated transport: flux vs concentration.
Comparing the solute flux vs initial concentration in Figure (PageIndex<13>), we see that there is a linear relationship for nonmediated transport, while mediated passive transport (and for that matter, active transport) shows a saturation effect due to the limiting factor of the number of available proteins to allow the solute through. Once there is enough solute to constantly occupy all transporters or channels, maximal ux will be reached, and increases in concentration cannot overcome this limit. This holds true regardless of the type of transporter protein involved, even though some are more intimately involved in the transport than others.
In addition to protein transporters, there are other ways to facilitate the movement of ions through membranes. Ionophores are small organic molecules, often (but not exclusively) made by bacteria, that help ions move through membranes. Many ionophores are antibiotics that act by causing the membranes to become leaky to particular ions, altering the electrochemical potential of the membrane and the chemical composition inside the cell. Ionophores are exclusively passive-transport mechanism, and fall into two types.
The first type of ionophore is a small mostly-hydrophobic carrier almost completely embedded in the membrane, that binds to and envelopes a speci c ion, shielding it from the lipid, and then moves it through the cell membrane. The most studied carrier-type ionophore is valinomycin, which binds to K+. Valinomycin is a 12-residue cyclic depsipeptide (contains amide and ester bonds) with alternating d- and l- amino acids. The carbonyl groups all face inward to interact with the ion, while the hydrophobic side chains face outward to the lipid of the membrane. Carrier ionophores are not necessarily peptides: the industrial chemical 2,4-dinitrophenol is an H + carrier and important environmental waste concern, and nystatin, an antifungal used to treat Candida albicans infections in humans, is a K + carrier.
The second type of carrier forms channels in the target membrane, but again, is not a protein. Gramicidin is a prototypical example, an anti-gram-positive antibacterial (except for the source of gramicidins, the gram-positive Bacillus brevis) and ionophore channel for monovalent cations such as Na + , K + , and H + . It is im- permeable to anions, and can be blocked by the divalent cation Ca 2+ . Like valinomycin, gramicidin A is also a made of alternating d- and l- amino acids, all of which are hydrophobic (l-Val/ Ile-Gly-l-Ala-d-Leu-l-Ala-d-Val-l-Val-d-Val-l-Trp-d-Leu-l-Trp-d-Leu- l-Trp-d-Leu-l-Trp). Gramicidin A dimerizes in the membrane to form a compressed b-sheet structure known as a b-helix. The dimerization forms N-terminal to N-terminal, placing the Trp res- idues towards the outer edges of the membrane, with the polar NH groups towards the extracellular and cytoplasmic surfaces, anchoring the pore in place.
Channels are essentially hands-off transport systems that, as the name implies, provides a passage from one side of the cell to another. Though channels may be gated - able to open and close in response to changes in membrane potential or ligand binding, for example - they allow solutes through at a high rate without tightly binding them and without changes in conformation. The solute can only move through channels from high to low concentration. The potassium channel depicted below (Figure (PageIndex<14>)A) is an example: there is a selectivity lter (14B) of aligned carbonyl oxygens that transiently positions the K+ ions for rapid passage through the channel, but it does not bind the K + for any significant period, nor does the channel undergo any conformational changes as a result of the interaction. Smaller Na + ions could (and on rare occasion do) make it through the K+ channel, but because they are too small to be properly positioned by the K + filter, they usually pop back out. It should be noted that this channel is a tetramer (14C) and the cutaway diagram in (14A) only shows half of the channel for clarity.
Figure (PageIndex<14>). (A) Half of the tetrameric K + channel showing two subunits. (B) Detail of the selectivity lter boxed in A. (C) Top-down image generated from data from the RCSB Protein Data Bank.
While most proteins called &ldquochannels&rdquo are formed by multiple alpha-helices, the porins are formed by a cylindrical beta sheet. In both cases, solutes can only move down the concentration gradient from high to low, and in both cases, the solutes do not make signi cant contact with the pore or channel. The interior of the pore is usually hydrophilic due to alternating hydrophilic/hydrophobic residues along the beta ribbon, which places the hydrophobic side chains on the outside, interacting with the membrane core.
Porins are primarily found in gram-negative bacteria, some gram-positive bacteria, and in the mitochondria and chloroplasts of eukaryotes. They are not generally found in the plasma membrane of eukaryotes. Also, despite the similarity in name, they are structurally unrelated to aquaporins, which are channels that facilitate the diffusion of water in and out of cells.
Transport proteins work very differently from channels or pores. Instead of allowing a relatively fast ow of solutes through the membrane, transport proteins move solutes across the membrane in discrete quanta by binding to the solute on one side of the membrane, changing conformation so as to bring the solute to the other side of the membrane, and then releasing the solute. These transport proteins may work with individual solute molecules like the glucose transporters, or they may move multiple solutes. The glucose transporters are passive transport proteins, so they only move glucose from higher to lower concentrations, and do not require an external energy source. The four isoforms are very similar structurally but differ in their tissue distribution within the animal: for example, GLUT2 is found primarily in pancreatic b cells, while GLUT4 is found mostly in muscle and fat cells.
On the other hand, the classic example of an active transport protein, the Na + /K + ATPase, also known as the Na + /K + antiport, utilizes the energy from ATP hydrolysis to power the conformational changes needed to move both Na + and K + ions against the gradient. Referring to the Figure (PageIndex<16>), in its resting state, the Na + /K + ATPase is open to the cytoplasm and can bind three Na + ions (1). Once the three Na + have bound, the transporter can catalyze the hydrolysis of an ATP molecule, removing a phosphate group and transferring it onto the ATPase itself (2). This triggers a conformational change that opens the protein to the extracellular space and also changes the ion binding site so that Na + no longer binds with high affinity and drops off (3). However, the ion binding site specificity is also altered in this conformational change, and these new sites have a high affinity for K + ions (4). Once the two K + bind, the attached phosphate group is released (5) and another conformational shift puts the transporter protein back into its original conformation, altering the K + binding sites to allow release of the K + into the cytoplasm (6), and revealing Na + affinity once again.
Figure (PageIndex<16>). Active Transport by Na + /K + ATPase. This enzyme pushes three Na + ions out of the cell and two K + ions into the cell, going against the gradient in both directions and using energy from ATP hydrolysis. [Note: some texts diagram this enzyme activity with separate binding sites for Na + and K + , but recent crystallographic evidence shows that there is only one ion binding site that changes conformation and specificity.]
The Na + /K + ATPase is a member of the P-type family of ATPases. They are named because of the autophosphorylation that occurs when ATP is hydrolyzed to drive the transport. Other prominent members of this family of ATPases are the Ca 2+ -ATPase that pumps Ca 2+ out of the cytoplasm into organelles or out of the cell, and the H + /K + ATPase, though there are also P-type H + pumps in fungal and plant plasma membranes, and in bacteria.
Cardiac glycosides (also cardiac steroids) inhibit the Na + /K + ATPase by binding to the extracellular side of the enzyme. These drugs, including digitalis (extracted from the purple foxglove plant) and ouabain (extracted from ouabio tree) are commonly prescribed cardiac medications that increase the intensity of heart contractions. The inhibition of Na + /K + ATPase causes a rise in [Na + ]in which then activates cardiac Na + /Ca 2+ antiports, pumping excess sodium out and Ca 2+ in. The increased [Ca 2+ ]cytoplasm is taken up by the sarcoplasmic reticulum, leading to extra Ca 2+ when it is released to trigger muscle contraction, causing stronger contractions.
Unlike Na + or K + , the Ca 2+ gradient is not very important with respect to the electro- chemical membrane potential or the use of its energy. However, tight regulation of Ca 2+ is important in a different way: it is used as an intracellular signal. To optimize the effectiveness of Ca 2+ as a signal, its cytoplasmic levels are kept extremely low, with Ca 2+ pumps pushing the ion into the ER (SR in muscles), Golgi, and out of the cell. These pumps are themselves regulated by Ca 2+ levels through the protein calmodulin. At low Ca 2+ levels, the pump is inactive, and an inhibitory domain of the pump itself prevents its activity. However, as Ca 2+ levels rise, the ions bind to calmodulin, and the Ca 2+ -calmodulin complex can bind to the inhibitory region of the Ca 2+ pump, relieving the inhibition and allowing the excess Ca 2+ to be pumped out of the cytoplasm.
There are three other families of ATPases: the F-type ATPases are proton pumps in bacteria and mitochondria and chloroplasts that can also function to form ATP by running &ldquobackwards&rdquo with protons owing through them down the concentration gradient. They will be discussed in the next chapter (Metabolism). Also, there are V-type ATPases that regulate pH in acidic vesicles and plant vacuoles, and finally, there are anion-transporting ATPases.
Figure (PageIndex<17>). Symport and Antiport. The terms refer only to direction of solutes in or out of cell, not to energetics. In this symport, the energy release from passive transport of Na + into the cell is used to actively transport glucose in also. In the antiport example, Na + transport is again used, this time to provide energy for active transport of H + out of the cell.
Hydrolysis of ATP, while a common source of energy for many biological processes, is not the only source of energy for transport. The active transport of one solute against its gradient can be coupled with the energy from passive transport of another solute down its gradient. Two examples are shown in Figure (PageIndex<17>): even though one is a symport (both solutes crossing the membrane in the same physical direction) and one is an antiport (the two solutes cross the membrane in opposite physical directions), they both have one solute traveling down its gradient, and one solute traveling up against its concentration gradient. As it happens, we have used Na + movement as the driving force behind both of these examples. In fact, the Na + gradient across the membrane is an extremely important source of energy for most animal cells. However this is not universal for all cells, or even all eukaryotic cells. In most plant cells and unicellular organisms, the H + (proton) gradient plays the role that Na + does in animals.
Acetylcholine receptors (AchR), which are found in some neurons and on the muscle cells at neuromuscular junctions, are ligand-gated ion channels. When the neurotransmitter (acetylcholine) or an agonist such as nicotine (for nicotinic type receptors) or muscarine (for muscarinic type receptors) binds to the receptor, it opens a channel that allows the ow of small cations, primarily Na + and K + , in opposite directions, of course. The Na + rush is much stronger and leads to the initial depolarization of the membrane that either initiates an action potential in a neuron, or in muscle, initiates contraction.
An ion is a molecule that is charged because it has lost or gained an electron. The cell membrane is made of a bilayer of phospholipids, with an inner and outer layer of charged,hydrophilic "heads" and a middle layer of fatty acid chains, which are hydrophobic, or uncharged. Charged ions cannot permeate the cell membrane for the same reason that oil and water don't mix: uncharged molecules repel charged molecules. Even the smallest of ions -- hydrogen ions -- are unable to permeate through the fatty acids that make up the membrane. If ions "want" to enter the cell due to a high concentration of that type of ion on one side of the cell, they can do so by entering through the protein channels that are embedded between the lipids.
2.6 Membrane Transport Overview
This section of the AP Biology curriculum – 2.6 Membrane Transport – covers the basics of how cells import and export the substances they need. We’ll start by looking at the differences between active and passive transport. Then, we’ll take a specific look at both passive transport (including diffusion and facilitated diffusion), and the energy-dependent modes of active transport. We’ll also take a look at how cells can take in large amounts of material via endocytosis and how cells can export large amounts of material via exocytosis.
The difference between active transport and passive transport is simple – active transport requires energy. As we will see, active transport can get this energy from ATP or it can utilize the potential energy stored in a concentration gradient. Active transport requires energy because it is moving a substance against the concentration gradient. In other words, the molecules are moving from an area of low concentration to an area of high concentration.
By contrast, passive transport does not require energy. No energy is needed because all forms of passive transport are moving molecules from an area of high concentration to an area of low concentration. Passive transport includes simple diffusion through the plasma membrane as well as facilitated diffusion through ion channels and carrier proteins. Let’s take a closer look at each of these modes of transport.
Passive transport does not require energy simply because molecules are moving in the direction they would be moving anyway – from high concentration to low concentration. There are two basic types of passive transport: simple diffusion and facilitated diffusion. Let’s take a closer look at simple diffusion.
Some molecules (like oxygen, water, and carbon dioxide) are small enough that they can pass right through the plasma membrane. Oxygen and carbon dioxide are nonpolar, uncharged molecules. This means that the hydrophobic core of the lipid bilayer does not effectively block them from passing through. While water is a polar molecule, it does not carry a charge. So, water can still slip through the plasma membrane when concentration gradients or pressure changes force it to move. When water moves across the membrane it is called osmosis, and we will take a closer look at this phenomenon in section 2.8. Now, let’s take a look at Facilitated Transport.
Facilitated transport is required for ions and large molecules. Ions cannot pass through the plasma membrane because they carry a charge and are blocked by the hydrophobic core. So, they must pass through hollow proteins known as channel proteins. Large molecules, such as glucose, are simply too large and polar to pass through the small gaps in the plasma membrane. These molecules are also too large for channel proteins, so they require a special carrier protein. These large molecules enter the carrier protein and bind to the active site – which changes the conformation of the protein. This change causes the protein to open on the other side of the membrane, releasing the molecule and resetting the process. We will cover both of these transport proteins further in section 2.7.
Active Transport requires energy because it is moving molecules from an area of low concentration to an area of high concentration. Unlike most forms of passive transport, active transport is directional – that is, it transports a specific substance in only one direction. There are three main types of proteins that engage in active transport.
A uniport (or sometimes uniporter) uses energy to actively pump 1 type of substance against its concentration gradient.
A symport (or symporter) moves two substances at the same time, in the same direction across the cell membrane. Some symporters are moving both molecules against their gradient, while others use the energy from one substance’s gradient to power the movement of another molecule against a gradient.
An antiport (or antiporter) moves two substances across the membrane but in opposite directions. Antiporters can also use one molecule’s gradient to power the movement of another molecule against the gradient.
There are two types of energy that can be used to power active transport: primary and secondary.
Primary active transport requires chemical energy from ATP or other energy-transporting molecules. The ATP molecule reacts with the transporter protein, removing a phosphate group and releasing energy into the protein’s molecular structure. This allows the protein to grab onto a substrate molecule and move it through the membrane against the concentration gradient.
By contrast, secondary active transport does not rely on chemical energy molecules like ATP. Instead, secondary active transport relies on the potential energy stored in a concentration gradient. For example, a sodium/calcium antiporter is using the energy stored in the sodium concentration gradient to move calcium against its concentration gradient. Three sodium molecules move into the antiporter, pushed by the concentration gradient. The antiporter then takes up one calcium ion. The energy from the sodium gradient forces a conformational change, forcing the calcium ion out of the cell against its concentration gradient!
Cells use a wide variety of integral membrane proteins to build up these chemical gradients and use them to power the movement of other substances across their cell membranes!
Next up, let’s look at some forms of membrane transport that are on a much larger scale than individual membrane proteins. Endocytosis and exocytosis are how the cell can import or export large amounts of material at the same time using large folds of the plasma membrane. The difference is simple to remember if you break down the words.
“Endo” means within or into, whereas cytosis refers to cells. So, Endocytosis means “into the cell”. Cells use endocytosis to take in large molecules, create food vesicles, and even “eat” smaller cells.
By contrast, “exo” means external or out of. So, Exocytosis means out of the cell. Cells use exocytosis to dump entire vesicles into the external environment.
Endocytosis and exocytosis are both forms of active transport because it takes a lot of energy to form vesicles and move them around the cell using the cytoskeleton. Let’s take a look at the different kinds of endocytosis and exocytosis.
There are three main types of endocytosis that cells use to intake large quantities of material: phagocytosis, pinocytosis, and receptor-mediated endocytosis.
Phagocytosis is how cells take in very large macromolecules and even smaller cells. For instance, entire bacterial cells can be eaten by white blood cells. The cell membrane wraps itself around the large object, then pinches off into a food vacuole. A lysosome will merge with the food vacuole, digesting its contents so the cell can use them.
Similarly, pinocytosis takes in a large quantity of water and substances by creating an inward fold of the cell membrane. The folds are generally much smaller than with phagocytosis. In this case, the cell simply sucks in water and smaller substances that are dissolved in water. This is a good way for a cell to take in a large quantity of water and nutrients at the same time.
But, cells can use receptor-mediated endocytosis to take in a large quantity of very specific substances. For instance, this is how your body transfers and recycles molecules like cholesterol, which would otherwise get stuck in the plasma membrane. Cholesterol is bonded to protein molecules, making lipoproteins. These lipoproteins can bind to specific receptors on the cell’s surface. When enough receptors have been activated, this entire portion of the cell membrane undergoes endocytosis. The vacuole merges with a liposome, it is digested completely, and the components of the original cholesterol can be recycled.
For the same reason that cells need to use entire portions of the cell membrane to intake substances, there are many uses for expelling substances with a similar process. This process is exocytosis. For instance, this is exactly what happens in your neurons every time they transfer a signal to the next neuron.
The nerve impulse comes through the presynaptic neuron, ending at the axon terminal. This causes vesicles full of neurotransmitters to bind with the cell membrane. These neurotransmitters are dumped into the synaptic space via exocytosis. The neurotransmitters quickly reach the next neuron and open ion channels. This disrupts the electrical balance of the cell membrane, causing a new nervous impulse to travel through the post-synaptic neuron.