Plasma Membrane Dynamics and Cell Transport Mechanisms

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Plasma Membrane Dynamics and Cell Transport Mechanisms

Plasma Membranes are mostly Lipids and Proteins arranged in a Fluid Mosaic Model

A typical cell membrane has a composition of:

Lipids: 40-60% - arranged in a double lipid bilayer.

Protein: 30-50% - proteins which are inserted either partly or completely through bilayer.

Carbohydrate: 5-10% - carbohydrates which attach to extracellular fluid (ECF) side.

These percentages can vary significantly depending on the specific type of cell in the body.

Plasma membrane

ECF ICF

Nucleus

Cytoplasm with organelles

Figure 1. This is the typical diagrammatic representation of a eukaryotic cell. The extracellular fluid (ECF) is kept separate from the intracellular fluid (ICF) by the plasma membrane.

General Function of Plasma Membranes

1. Physical Barrier: The plasma membrane (PM) acts as a barrier; it separates the inside of the cell, containing ICF, from the outside of the cell, containing ECF. It creates the boundary of the cell andisolates it from other cells and structures.

1. Regulation of Exchange: Anything that goes into or out of a cell must do so by crossing the plasma membrane. Exchange with the environment occurs across this membrane, either by slipping through the membrane or by being transported across by protein channels or protein carriers.

1. Structural Support: Structural proteins are tethered to the internal or intracellular aspect of the plasma membrane in order to create the internal structural support for the cell. This internal framework is referred to as the cytoskeleton of the cell. For example, this helps create the shape of cells, like the distinctive biconcave disc shape of the red blood cell.

1. Communication and Cell ID: Signals from the external environment of the cell are transferred into the internal compartment across the plasma membrane. This often involves receptors that sit on the external aspect of the plasma membrane to receive the signal. Signal molecules are called ‘ligands’ and they bind to receptors, much like substrates bind to enzymes. There are also molecules (glycoproteins and glycolipids) which attach to the external surface of the plasma membrane to help identify the cell as self. For example, these flags or markers are what make up the blood typing of a red blood cell (A, B, AB or O).

Membrane Lipids

1. Phospholipids - usually about 75% of lipid content.

The polar glycerol-phosphate head of a phospholipid is the hydrophilic end and a nonpolar fatty acid tail is the hydrophobic end. The entire molecule is amphiphilic, meaning it can mix with both water and lipid environments.The phospholipids are arranged in two rows, called the lipid bilayer andthis functions as a barrier that only lipid-soluble molecules can penetrate. They also provide a framework for membrane proteins. Some lipids are involved in cellular communication. Some common phospholipids found in plasma membranes include phosphatidyl choline and sphingomyelin.

2. Cholesterol - usually about 20 - 30% of lipid content.

This 4 ringed lipid structure inserts into the hydrophobic center with the nonpolar fatty acid tails. The more cholesterol in the plasma membrane the more insulative the membrane will be. For example, the myelin sheath membrane (which insulates axons of nerve cells) is about 30%cholesterol, while other mammalian cell membranes may be about20% cholesterol.

Cholesterol helps to stabilize the plasma membrane. It functions to keep membranes impermeable and yet flexible. Membranes with higher cholesterol concentrations are less permeable to ions, water, and other small molecules. Presumably cholesterol blocks the openings between phospholipid tails through which these small molecules could otherwise pass. Mammals maintain a relatively constant Tb, so the "plasticizing" effect of cholesterol is not as important as it is inpoikilothermic animals and plants that cannot maintain a constant body temperature.

3. Glycolipids – usually about 5% of the lipid content.

The prefix glyco means ‘glucose’ or ‘sugar’, so a glycolipid is a small amount of a sugar attached to a large amount of lipid. Glycolipids are found on the external surface of the plasma membraneand act as a cell markers. This helps identify the cell as self to defense cells of the body.

Other Phospholipid Arrangements

1.Micelles are small droplets with hydrophobic tails forming the interior; the hydrophilic heads form the exposed boundary. Important in digestion and absorption of fats in digestive tract.

2.Liposomes are larger hollow spheres with phospholipid bilayer walls. Their hollow core can be loaded with water-soluble molecules. Can be used as a drug delivery system.

Membrane Carbohydrates

Plasma membrane carbohydrates attach to both lipids and proteins. The Glycocalyx is a protective layer on cell surface formed by Glycoproteins - when glucose attached to membrane proteins and Glycolipids - when glucose attached to membrane lipids. The carbohydrates of the glycocalyx play a critical role in identifying cells; for example, the carbohydrates of the glycocalyx in human blood cells differentiate the main ABO blood groups from one another.

Membrane Proteins

1. Associated Proteins

Also termed peripheral or extrinsic proteins. They are attached loosely to membrane-spanning proteins or to polar regions of phospholipids. They do not span the plasma membrane!

2. Integral ProteinsandMembrane-Spanning Proteins

Also termed intrinsic proteins. These are tightly bound into the phospholipid bilayer. Some integral proteins only extend partway into the membrane, others are membrane-spanning. Membrane-spanning proteins have segments that cross the membrane multiple times. Loops extend into extracellular and intracellular regions. Carbohydrates attach to extracellular loops and phosphates attach to intracellular loops. When amino acids are linked to each other, they can form an -helix that has an exterior layer of nonpolar side groups and a central core composed of the polar amino and carboxyl groups. This ties the protein so firmly to the membrane that it can only be freed by disrupting the phospholipid bilayer with detergents.

Membrane receptors, transporters, and enzymes are grouped into families according to how many membrane-spanning regions they possess. Below are some examples:

1)The voltage-gated K+ channel has six transmembrane segments.

2)The voltage-gated Na+ and Ca2+ channels have four associated segments (domains), each with six membrane-spanning regions.

3)The ATPase transporters of eukaryotic cells have 8-10 membrane-spanning regions.

4)The G-protein-linked membrane receptors all have seven transmembrane segments, as do the 2-adrenergic and rhodopsin receptors.

Originally it was thought that membrane proteins all floated freely within the lipid layer of the membrane. However, it has been shown that some proteins are immobile, held in place by cytoskeleton proteins. Restriction of protein movement allows membrane polarity, which can be seen in transporting epithelia. Other proteins are mobile and move under the direction of cytoskeleton. For example, rhodopsin, the protein pigment that absorbs light in the retina, rotates in place, somersaulting at a rate of 60° every 10 seconds.

3. Glycoproteins

As mentioned above, the prefix glyco means ‘glucose’, so a glycoprotein is a small amount of a carbohydrate (sugar) attached to a large amount of protein. If the molecule is called a proteoglycan, then there is more sugar (glyco) than protein. Glycoproteins are also found on the external surface of the plasma membrane and act as a cell markers.

Function of Plasma Membrane Proteins

The proteins that are associated with the plasma membrane have an expansive range of roles.

1. Structural Elements
2. Cell Adhesion Molecules
3. Enzymes
4. Receptors
5. Transporters

1. Structural Proteins–Theses link cytoskeleton and membrane to maintain cell shape, e.g., microvilli, red blood cells. The characteristic shape of the red blood cell is due to an extensive cytoskeleton that pulls the cell membrane into a biconcave disc shape. In diseases such as hereditary spherocytosis, defects in cytoskeletal proteins produce abnormally shaped red blood cells that are unable to move normally through the circulatory system.

2. Cell Adhesion Molecules - Form part of the cell-to-cell connections holding tissues together. Membrane-spanning proteins link the cytoskeleton to the extracellular matrix. The most common fibrous protein that attachesa cell to adjacent cells is collagen!

3. Enzymes – Membrane associated enzymes act as any other enzymes do but are fixed to the plasma membrane. Chemical reactions can take place on either membrane face, i.e. on the extracellular orintracellular surface. For example, enzymes on luminal surface in small intestine cells (extracellular) digest peptides and carbohydrates. Enzymes on the intracellular surface, such as adenylyl cyclase, play an important role in signal transduction.

4. Receptors –These act as receivers for the body's chemical signaling system, with each receptor being specific for a certain type or family of signal molecule. A ligand is any molecule binding to a receptor. Ligand binding usually triggers another membrane event, this can be signal transduction (e.g., hormone binding) or directly lead to an ion channel opening or closing (ionotropic effect).

5. Transporters - Many molecules require the use of transporters to cross cell membranes. Most lipophobic (can also be termed hydrophilic)molecules, such as smaller carbohydrates, amino acids, peptides, proteins, and charged particles such as ions, must have assistance from membrane proteins in order to get into or out of cells.

All of the above listed functions of plasma membrane proteins are very important. In the next stage that follows, however, we are going concentrate on the role of plasma membrane proteinsas transporters in the body and the various mechanisms by which they move molecules from one side of the plasma membrane tothe other.

There are 2 Categories of Protein Transporters: Protein Channels and Protein Carriers

Protein Channels

Protein channelsare well named; they are much like little water-filled channels, forming a passageway that directly links the ECF to ICF. The narrow diameter of protein channels restricts passage through them to small sized molecules, mostly water (H2O) and ions(K+, Na+, Cl- and Ca2+). Electrical charges lining the inner channel may restrict the movement of some molecules;therefore they can be very specific as to what they allow to travel through them. This mode of transport is very fast, much faster than protein carriers because there is no need for the binding of the substrate as in protein carriers.

ECFICF

Will this get through? Yes, it is small enough.

protein

channel

Will this get through? No, it is too big.

plasma

membrane

Open channels spend most time in the open configuration andare also called pores. Other channels are gated and spend most time in a closed state.

Three Types of Gated Ion Channels:

The protein channels that have gates that can open or close are called gated ion channels. There are three types of gated channels that we will explore, and they differ in the ‘trigger’ that opens or closes the gate, they are:

1. Chemically GatedChannels: triggered by specific ligands (chemicals)to open or close channel.

1. Voltage-GatedChannels: triggered by electrical changes across cellto open or closechannel.

1. Mechanically GatedChannels: triggered by distention or physical force to open or close channel.

Some gated channels remain open and the molecules leak across the channel, these are often called "leaky channels". The normal permeability of cells to Na+ and K+ is due to such leak channels.

Protein Carriers

The second type of protein transporters are called protein carriers. These never form a direct or continuous passage between the ECF and the ICF. They have a binding site (like enzymes) and will only transport specific moleculesthat match this site. Once the molecule binds to the site, the protein carrier undergoes a conformation (shape) change. It can rotate, or close one end while it opens the opposite, thus carrying the molecule across membrane. This mode of transportation is slower than protein channels, as they need to bind the substrate and change shape while moving substrates.

ECFICF

Will this get through? Yes, it has the right shape forbinding site.

ProteinTypically, carriers are used for transporting larger, polar molecules.

carrier

A perfect example is glucose. Glucose has a MW of 180, so it is a larger molecule, but not massive like starch or albumin. It is also a polar molecule, meaning it is soluble (mixes) in water. Amino acids are another good example of molecules moved by carriers.

Properties of Protein CarrierMediated Transport

Because of the way that protein carriers work, their transportexhibits saturation, specificity, and competition.

Specificity

Protein carriers move only one type or family of closely related molecules. For example, GLUT transporters move glucose, mannose, galactose, and fructose across membranes. They are specific for naturally occurring 6-carbon monosaccharides. Other carriers will transport amino acids, and there can be up to 20 different types of carriers, each specific for the 20 different amino acids the human body uses.

Competition

Carriers have preference (or affinity) for certain molecule(s). This can result in competition for the binding site between various molecules. For example, maltose is a disaccharide made of 2 glucose molecules, so one end of the maltose could try to occupy the binding sitefor a glucose transporter. Although it can bind, typically it will not be transportedin the process, it is not the right shape overall. Thus in this case, maltose would be a competitive inhibitor for glucose transport.

Saturation

Saturation occurs when a group of protein carriersare transporting the substrate at its maximum rate, with all carriers occupied. Saturation will depend on the number of available carriers and substrate concentration. Cells can sometimes increase or decrease the number of available carriers to control substrate movement. As the substrate concentration increases, transport rate increases until the carriers become saturated. At this stage they are at their maximum transport capacity and cannot move things across the membrane any faster.

An interesting consequence of saturation can be seen in the transport of glucose in the kidney. Normally, you should not find any glucose in your urine. If you do, it can be a sign of diabetes mellitus. However, if you were to consume large quantities of glucose, say by eating too many chocolates from your valentine gift, you may have glucose in your urine that is not due to a disease state (not yet anyway!). The glucose carriers in your kidney tubules can become saturated due to the abnormally high amounts of glucose being filtered by your renal system. If the carriers reach their maximum and more glucose is still in the filtrate, it will end up in the urine due to protein carrier saturation.

MOVEMENT ACROSS MEMBRANES

You may have heard plasma membranes described as selectively or semi-permeablemembranes. This means that some molecules can get across and some molecules cannot. The membrane composition determines which molecules move across. Permeable molecules can cross membrane by any method. Impermeable molecules cannot cross cell membrane.

General Factors Influencing Molecule Permeability

Although the components of a plasma membrane can vary, the properties of a given molecule will have a large effect on whether is passes through the plasma membrane easily, or if it needs assistance or if it cannot pass at all.

1. Size of molecule – smaller molecules can more easily pass through than larger.

2.Polarity or lipid solubility of molecule – lipid soluble molecules pass through more easily than polar.

3. Charge of molecule – uncharged molecules pass through more easily than charged.

The permeability of a molecule can be influenced by all three of these factors, not just one. For example, water (H2O) is a polar molecule, that is, it is insoluble (does not mix) in lipids. This would tend to make it less permeable, since the phospholipid bilayer creates a significant barrier to polar substances crossing the membrane.However, the molecular weight (MW) of H2O is only 18, thus it is very small and for this reason can easily pass through most cell membranes in the human body.

Ions are commonly very small, but they are charged particles and cannot pass directly through membrane by simple diffusion, they would require a protein channel,they would require a protein channel. At the other end of the spectrum, just because a molecule is fairly large does not mean it cannot pass directly through membrane by simple diffusion; relatively larger lipophilic substances can cross directly through membrane by simple diffusion, as the lipid bilayer is not a barrier. Very large molecules or a large amount of substance will typically requiremembrane transportation in a vesicle (see below).

There are 2 ways a molecule can transported across a cell membrane: Passive & Active

1. Passive Transport: does not require energy (ATP). Movement down a gradient.

1) Diffusion

2) Facilitated diffusion

3) Filtration

1) Diffusion

Diffusion is the net movement of molecules from an area of higher concentration to an area of lower concentration. In other words, the molecule is moving down its concentration gradient. This is a passive transport mechanism.Getting in a kayak and going down stream with the river is an example of passive transport. No energy expenditure is required; you can just sit there and be moved down stream. In the body, the net movement of molecules continues down its gradient until equilibriumis reached.Diffusion can occur in open regions or across a partition such as a membrane.

Factors that Effect the Rate of Diffusion

Diffusion is a very common and important mode of transport in the human body. The oxygen (O2) that enters our blood stream from our lungs does so by simple diffusion. A very important issue in human physiology is what factors affect the rate of diffusion of a molecule from one side of a plasma membrane to the other. Listed below are some of the important factors that affect the rate (how quickly) diffusion takes place.