5. Cell Membranes and Signaling. Chapter 5 Cell Membranes and Signaling. Key Concepts 5.1 Biological Membranes Have a Common Structure and Are Fluid 5.2 Some Substances Can Cross the Membrane by Diffusion 5.3 Some Substances Require Energy to Cross the Membrane.
5.4 Large Molecules Cross the Membrane via Vesicles
5.5 The Membrane Plays a Key Role in a Cell’s Response to Environmental Signals
5.6 Signal Transduction Allows the Cell to Respond to Its Environment
What role does the cell membrane play in the body’s response to caffeine?
A membrane’s structure and functions are determined by its constituents: lipids, proteins, and carbohydrates.
The general structure of membranes is known as the fluid mosaic model.
Phospholipids form a bilayer which is like a “lake” in which a variety of proteins “float.”
Lipids form the hydrophobic core of the membrane.
Most lipid molecules are phospholipids with two regions:
A bilayer is formed when the fatty acid “tails” associate with each other and the polar “heads” face the aqueous environment.
Bilayer organization helps membranes fuse during vesicle formation and phagocytosis.
Membranes may differ in lipid composition as there are many types of phospholipids.
Phospholipids may differ in:
Fatty acid chain length
Degree of saturation
Kinds of polar groups present
Two important factors in membrane fluidity:
Lipid composition—types of fatty acids can increase or decrease fluidity
Temperature—membrane fluidity decreases in colder conditions
Biological membranes contain proteins, with varying ratios of phospholipids.
Peripheral membrane proteins lack hydrophobic groups and are not embedded in the bilayer.
Integral membrane proteins are partly embedded in the phospholipid bilayer.
Anchored membrane proteins have lipid components that anchor them in the bilayer.
Proteins are asymmetrically distributed on the inner and outer membrane surfaces.
A transmembrane protein extends through the bilayer on both sides, and may have different functions in its external and transmembrane domains.
Some membrane proteins can move within the phosopholipid bilayer, while others are restricted.
Proteins inside the cell can restrict movement of membrane proteins, as can attachments to the cytoskeleton.
Plasma membrane carbohydrates are located on the outer membrane and can serve as recognition sites.
Glycolipid—a carbohydrate bonded to a lipid
Glycoprotein—a carbohydrate bonded to a protein
Membranes are constantly changing by forming, transforming into other types, fusing, and breaking down.
Though membranes appear similar, there are major chemical differences among the membranes of even a single cell.
Biological membranes allow some substances, and not others, to pass. This is known as selective permeability.
Two processes of transport:
Passive transport does not require metabolic energy.
Active transport requires input of metabolic energy.
Passive transport of a substance can occur through two types of diffusion:
Simple diffusion through the phospholipid bilayer
Facilitated diffusion through channel proteins or aided by carrier proteins
Diffusion is the process of random movement toward equilibrium.
Speed of diffusion depends on three factors:
Diameter of the molecules—smaller molecules diffuse faster
Temperature of the solution—higher temperatures lead to faster diffusion
The concentration gradient in the system—the greater the concentration gradient in a system, the faster a substance will diffuse
A higher concentration inside the cell causes the solute to diffuse out, and a higher concentration outside causes the solute to diffuse in, for many molecules.
Simple diffusion takes place through the phospholipid bilayer.
A molecule that is hydrophobic and soluble in lipids can pass through the membrane.
Polar molecules do not pass through—they are not soluble in the hydrophilic interior and form bonds instead in the aqueous environment near the membrane.
Osmosis is the diffusion of water across membranes.
It depends on the concentration of solute molecules on either side of the membrane.
Water passes through special membrane channels.
When comparing two solutions separated by a membrane:
A hypertonic solution has a higher solute concentration.
Isotonic solutions have equal solute concentrations.
A hypotonic solution has a lower solute concentration.
The concentration of solutes in the environment determines the direction of osmosis in all animal cells.
In other organisms, cell walls limit the volume that can be taken up.
Turgor pressure is the internal pressure against the cell wall—as it builds up, it prevents more water from entering.
Diffusion may be aided by channel proteins.
Channel proteins are integral membrane proteins that form channels across the membrane.
Substances can also bind to carrier proteins to speed up diffusion.
Both are forms of facilitated diffusion.
Ion channels are a type of channel protein—most are gated, and can be opened or closed to ion passage.
A gated channel opens when a stimulus causes the channel to change shape.
The stimulus may be a ligand, a chemical signal.
Aligand-gated channel responds to its ligand.
A voltage-gated channel opens or closes in response to a change in the voltage across the membrane.
Water crosses membranes at a faster rate than simple diffusion.
It may “hitchhike” with ions such as Na+ as they pass through channels.
Aquaporins are specific channels that allow large amounts of water to move along its concentration gradient.
Carrier proteins in the membrane facilitate diffusion by binding substances.
Glucose transporters are carrier proteins in mammalian cells.
Glucose molecules bind to the carrier protein and cause the protein to change shape—it releases glucose on the other side of the membrane.
Transport by carrier proteins differs from simple diffusion, though both are driven by the concentration gradient.
The facilitated diffusion system can become saturated—when all of the carrier molecules are bound, the rate of diffusion reaches its maximum.
Active transport requires the input of energy to move substances against their concentration gradients.
Active transport is used to overcome concentration imbalances that are maintained by proteins in the membrane.
The energy source for active transport is often ATP.
Active transport is directional and moves a substance against its concentration gradient.
A substance moves in the direction of the cell’s needs, usually by means of a specific carrier protein.
Two types of active transport:
Primary active transport involves hydrolysis of ATP for energy.
Secondary active transport uses the energy from an ion concentration gradient, or an electrical gradient.
The sodium–potassium (Na+–K+) pump is an integral membrane protein that pumps Na+ out of a cell and K+ in.
One molecule of ATP moves two K+ and three Na+ ions.
Secondary active transport uses energy that is “regained,” by letting ions move across the membrane with their concentration gradients.
Secondary active transport may begin with passive diffusion of a few ions, or may involve a carrier protein that transports both a substance and ions.
Macromolecules are too large or too charged to pass through biological membranes and instead pass through vesicles.
To take up or to secrete macromolecules, cells must use endocytosis or exocytosis.
Three types of endocytosis brings molecules into the cell: phagocytosis, pinocytosis, and receptor–mediated endocytosis.
In all three, the membrane invaginates, or folds around the molecules and forms a vesicle.
The vesicle then separates from the membrane.
In phagocytosis (“cellular eating”), part of the membrane engulfs a large particle or cell.
A food vacuole (phagosome) forms and usually fuses with a lysosome, where contents are digested.
In pinocytosis (“cellular drinking”), vesicles also form.
The vesicles are smaller and bring in fluids and dissolved substances, as in the endothelium near blood vessels.
Receptor–mediated endocytosis depends on receptors to bind to specific molecules (their ligands).
The receptors are integral membrane proteins located in regions called coated pits.
The cytoplasmic surface is coated by another protein (often clathrin).
When receptors bind to their ligands, the coated pit invaginates and forms a coated vesicle.
The clathrin stabilizes the vesicle as it carries the macromolecules into the cytoplasm.
Once inside, the vesicle loses its clathrin coat and the substance is digested.
Exocytosis moves materials out of the cell in vesicles.
The vesicle membrane fuses with the plasma membrane and the contents are released into the cellular environment.
Exocytosis is important in the secretion of substances made in the cell.
Cells can respond to many signals if they have a specific receptor for that signal.
A signal transduction pathway is a sequence of molecular events and chemical reactions that lead to a cellular response, following the receptor’s activation by a signal.
Cells are exposed to many signals and may have different responses:
Autocrine signals affect the same cells that release them.
Paracrine signals diffuse to and affect nearby cells.
Hormones travel to distant cells.
Only cells with the necessary receptors can respond to a signal—the target cell must be able to sense it and respond to it.
A signal transduction pathway involves a signal, a receptor, and a response.
A common mechanism of signal transduction is allosteric regulation.
This involves an alteration in a protein’s shape as a result of a molecule binding to it.
A signal transduction pathway may produce short or long term responses.
A signal molecule, or ligand, fits into a three-dimensional site on the receptor protein.
Binding of the ligand causes the receptor to change its three-dimensional shape.
The change in shape initiates a cellular response.
Ligands are generally not metabolized further, but their binding may expose an active site on the receptor.
Binding is reversible and the ligand can be released, to end stimulation.
An inhibitor, or antagonist, can bind in place of the normal ligand.
Receptors can be classified by their location in the cell.
This is determined by whether or not their ligand can diffuse through the membrane.
Cytoplasmic receptors have ligands, such as estrogen, that are small or nonpolar and can diffuse across the membrane.
Membrane receptors have large or polar ligands, such as insulin, that cannot diffuse and must bind to a transmembrane receptor at an extracellular site.
Receptors are also classified by their activity:
Ion channel receptors
Protein kinase receptors
G protein–linked receptors
Ion channel receptors, or gated ion channels, change their three-dimensional shape when a ligand binds.
The acetylcholine receptor, a ligand-gated sodium channel, binds acetylcholine to open the channel and allow Na+ to diffuse into the cell.
Protein kinase receptors change their shape when a ligand binds.
The new shape exposes or activates a cytoplasmic domain that has catalytic (protein kinase) activity.
Protein kinases catalyze the following reaction:
ATP + protein ADP + phosphorylated protein
Each protein kinase has a specific target protein, whose activity is changed when it is phosphorylated.
Ligands binding to G protein–linked receptors expose a site that can bind to a membrane protein, a G protein.
The G protein is partially inserted in the lipid bilayer, and partially exposed on the cytoplasmic surface.
Many G proteins have three subunits and can bind three molecules:
GDP and GTP, used for energy transfer
An effector protein to cause an effect in the cell
The activated G protein–linked receptor exchanges a GDP nucleotide bound to the G protein for a higher energy GTP.
The activated G protein activates the effector protein, leading to signal amplification.
Signal activation of a specific receptor leads to a cellular response, which is mediated by a signal transduction pathway.
Signaling can initiate a cascade of protein interactions—the signal can then be amplified and distributed to cause different responses.
A second messenger is an intermediary between the receptor and the cascade of responses.
In the fight-or-flight response, epinephrine (adrenaline) activates the liver enzyme glycogen phosphorylase.
The enzyme catalyzes the breakdown of glycogen to provide quick energy.
Researchers found that the cytoplasmic enzyme could be activated by the membrane-bound epinephrine in broken cells, as long as all parts were present.
They discovered that another molecule delivered the message from the “first messenger,” epinephrine, to the enzyme.
The second messenger was later discovered to be cyclic AMP (cAMP).
Second messengers allow the cell to respond to a single membrane event with many events inside the cell—they distribute the signal.
They amplify the signal by activating more than one enzyme target.
Signal transduction pathways involve multiple steps—enzymes may be either activated or inhibited by other enzymes.
In liver cells, a signal cascade begins when epinephrine stimulates a G protein–mediated protein kinase pathway.
Epinephrine binds to its receptor and activates a G protein.
cAMP is produced and activates protein kinase A—it phosphorylates two other enzymes, with opposite effects:
Inhibition—protein kinase A inactivates glycogen synthase through phosphorylation, and prevents glucose storage.
Activation—Phosphorylase kinase is activated when phosphorylated and is part of a cascade that results in the liberation of glucose molecules.
Signal transduction ends after the cell responds—enzymes convert each transducer back to its inactive precursor.
The balance between the regulating enzymes and the signal enzymes determines the cell’s response.
Cells can alter the balance of enzymes in two ways:
Synthesis or breakdown of the enzyme
Activation or inhibition of the enzymes by other molecules
Cell functions change in response to environmental signals:
Opening of ion channels
Alterations in gene expression
Alteration of enzyme activities
Caffeine is a large, polar molecule that binds to receptors on nerve cells in the brain.
Its structure is similar to adenosine, which binds to receptors after activity or stress and results in drowsiness.
Caffeine binds to the same receptor, but does not activate it—the result is that the person remains alert.