Plasma Membrane PDF

Plasma Membrane Plasma Membrane: Structure The cell membrane (also known as the plasma membrane or plasmalemma) is approximately 7.5-10 nm thick and consists of an inner and an outer leaflet, known as the phospholipid bilayer, and its integral and peripheral proteins. The inner leaflet fac...

Plasma Membrane Plasma Membrane: Structure The cell membrane (also known as the plasma membrane or plasmalemma) is approximately 7.5-10 nm thick and consists of an inner and an outer leaflet, known as the phospholipid bilayer, and its integral and peripheral proteins. The inner leaflet faces the cytoplasm, and the outer leaflet contacts the extracellular environment. Viewed by transmission electron microscopy (TEM), the cell membrane displays a trilaminar structure, referred to as the unit membrane. Plasma Membrane: Function Maintains the cell's structural and functional integrity. Acts as a semipermeable membrane, restricting movement of material between the cytoplasm and the external environment. Assists in the recognition of macromolecules and other cells as well as allows the cell to be recognized by other cells; it also controls interaction between cells. Assists in the transduction of extracellular signals into intracellular events. Maintains a potential difference between the cytoplasmic and extracellular sides. CELL MEMBRANE FLUID MOSAIC MODEL The phospholipid bilayer is composed of phospholipids, sphingolipids, glycolipids, and cholesterol. It is freely permeable to small, lipid-soluble, nonpolar molecules but is impermeable to charged ions and large molecules. The various types of phospholipids, the major component of the phospholipid bilayers, are amphipathic molecules, consisting of a polar (hydrophilic) head and two nonpolar (hydrophobic) fatty acid (acyl) tails, one of which is usually unsaturated. The polar head of each molecule faces the membrane surface, whereas the tails project into the interior of the membrane, so they face each other. The leaflet tails are mostly 16 to 18 carbon chain fatty acids, and they form weak noncovalent bonds that attach the two leaflets to each other. Phospholipid distribution is asymmetrical in the two leaflets.  Glycolipids are restricted to the extracellular aspect of the outer leaflet. Polar carbohydrate residues of glycolipids extend from the outer leaflet into the extracellular space and form part of the glycocalyx. Cholesterol, only 2% of plasmalemma lipids, is present in both leaflets and helps maintain the structural integrity of the membrane. Cholesterol regulates the fluidity of the membrane by inserting itself between phospholipid molecules. At higher temperatures, it restricts excessive movement of these phospholipids, keeping the membrane stable. At lower temperatures, it prevents them from packing too tightly, which keeps the membrane fluid. Cholesterol adds strength to the membrane by providing a more organized and less permeable structure. Cholesterol creates specialized microdomains known as lipid rafts. These rafts concentrate certain membrane proteins and lipids, facilitating cell signaling and membrane protein trafficking, which are critical for cellular communication.  Membrane proteins are of two types: integral proteins and peripheral proteins. In most cells, they constitute 50% of the plasma membrane composition, although in some instances, as in myelin, the ratio can be as little as 25%. Some membrane proteins diffuse laterally in the phospholipid bilayer; others are immobile and are held in place by cytoskeletal components. Integral proteins are embedded in the phospholipid bilayer. Transmembrane proteins, composed mostly of glycoproteins, span the entire cell membrane thickness and may function as/in membrane receptors, enzymes, cell adhesion molecules, cell recognition proteins, signal transduction, and transport proteins. Transmembrane proteins are amphipathic, with some hydrophilic and hydrophobic amino acids that interact with the hydrocarbon tails of the membrane phospholipids. Most transmembrane proteins are multipass proteins: they are folded in such a fashion that they pass back and forth across the plasmalemma several times. Integral proteins can be anchored to the inner (or occasionally outer) leaflet via fatty acyl or prenyl groups. In freeze-fracture preparations, integral proteins remain preferentially attached to the P- face, the outer (protoplasmic face) surface of the inner leaflet, rather than to the E-face (extracellular face).  Peripheral proteins are located either on the cytoplasmic or on the extracellular aspects of the cell membrane but do not enter the phospholipid bilayer. Covalently linked glycolipids on the external aspect of the plasmalemma act as anchors for peripheral proteins, which then extend into the extracellular space. Commonly, carbohydrates may bind to the peripheral proteins located on the extracellular aspect of the plasmalemma, forming glycoproteins. Peripheral proteins may also bind to the phospholipid polar groups or integral proteins of the membrane via noncovalent interactions; in this case, they function as electron carriers (e.g. cytochrome c), as part of the cytoskeleton, or as part of an intracellular second messenger system. Among these peripheral proteins are a group of anionic, calcium-dependent, lipid- binding proteins known as annexins, which act to modify the relationships of other peripheral proteins with the phospholipid bilayer and also to function in membrane trafficking and the formation of ion channels; synapsin I, which binds synaptic vesicles to the cytoskeleton; and spectrin, which stabilizes cell membranes of erythrocytes. Glycocalyx (cell coat), located on the outer surface of the outer leaflet of the plasma lemma, varies in appearance (fuzziness) and thickness (up to 50 nm). It consists of polar oligosaccharide side chains as well as proteoglycans. The oligosaccharides are linked covalently to most proteins and some lipids (glycolipids) of the plasmalemma. Glycocalyx Functions Aids in attachment of some cells (e.g. fibroblasts but not epithelial cells) to extracellular matrix components. Binds antigens and enzymes to the cell surface. Facilitates cell-cell recognition and interaction. Protects cells from injury by preventing contact with inappropriate substances. Assists T cells and antigen-presenting cells in aligning with each other in the proper fashion and aids in preventing inappropriate enzymatic cleavage of receptors and ligands. Lines (in blood vessels) the endothelial surface to decrease frictional forces as the blood rushes by, diminishes loss of fluid from the vessel, and inhibits coagulation. CELL MEMBRANE TRANSPORT PROCESSES Uniport - transport of a single molecule Symport - cotransport of two different molecules in the same direction. Antiport - cotransport of two different molecules in the opposite direction. Passive transport Passive transport includes simple and facilitated diffusion. Neither of these processes requires energy because molecules move across the cell membrane down a concentration or electrochemical gradient. Simple diffusion Simple diffusion is the transport of small nonpolar molecules ( e.g. O2 and N2) and small, uncharged polar molecules ( e.g. H20, CO2, and glycerol) directly across the cell membrane without the need for ion channels or carrier proteins. It exhibits little specificity for the transported molecule, and the diffusion rate is proportional to the concentration gradient of the diffusing molecule. Facilitated diffusion Facilitated diffusion occurs via ion channels and/or carrier proteins, structures that exhibit specificity for the transported molecules. Not only is it faster than simple diffusion, but it is also responsible for providing a pathway for ions and large polar molecules to traverse membranes that would otherwise be impermeable to them. Ion channel proteins are multipass transmembrane proteins that form small aqueous pores designed to permit specific small water-soluble molecules and ions, such as Cl-, to pass down an electrochemical gradient (passive transport). Aquaporins are channels designed for the rapid transport of water across the cell membrane without permitting an accompanying flow of protons to pass through the channels. Aquaporins force water molecules to flip-flop halfway down the channel, so that water molecules enter with their oxygen leading into the channel and leave with their oxygen trailing the hydrogen atoms. Carrier proteins are multipass transmembrane proteins that undergo reversible conformational changes to transport specific molecules across the membrane; these proteins function in both passive transport and active transport. Ionophores Facilitated diffusion of ions can occur via ion channel proteins or ionophores. Selective ion channel proteins permit only specific ions to traverse them. These channels may be ungated (i.e. they are always open) or gated. K+ leak channels are the most common ion channels. These channels are ungated and leak K+, the ions most responsible for establishing a potential difference across the plasmalemma. Gated ion channels open only transiently in response to various stimuli. They include the following types: Voltage-gated channels open only when the potential difference across the membrane changes (e.g. voltage-gated Na+ channels), which function in the generation of action potentials. Mechanically gated channels open in response to a mechanical stimulus ( e.g. the tactile response of the hair cells in the inner ear). Ligand-gated channels open in response to the binding of a signaling molecule or ion. These channels include neurotransmitter-gated channels, nucleotide-gated channels, and G protein-gated K+ channels of cardiac muscle cells. Active transport Active transport is an energy-requiring process that transports a molecule against an electrochemical gradient via carrier proteins. Na+-K+pump is a carrier protein that transports Na+ and K+ ions in opposite directions (anti port) mediated by Na+-K+ adenosine triphosphatase (ATPase ). Three Na+ ions are pumped out of the cell, and two K+ ions are pumped into the cell using the energy from the hydrolysis of a single ATP molecule by the ATPase. The primary function is to maintain constant cell volume by decreasing the intracellular ion concentration (and thus the osmotic pressure) and increasing the extracellular ion concentration, thus decreasing the flow of water into the cell. The Na - K pump also plays a minor role in the maintenance of a potential difference across the cell membrane. Glucose transport involves the symport movement of glucose across an epithelium (transepithelial transport). Transport is frequently along an electrochemical Na+ gradient, via carrier proteins.  ATP-binding cassette transporters (ABC transporters) are transmembrane proteins that have two domains, the intracellularly facing nucleotide-binding domain (ATP-binding domain) and the membrane-spanning domain (transmembrane domain). In eukaryotes, ABC transporters use ATP to exocytose materials, such as toxins and drugs, from the cytoplasm into the extracellular space. ABC transporters may have additional functions, such as those of the placenta, which protect the developing fetus from xenobiotics (macromolecules such as antibiotics), not manufactured by cells of the mother. CELL-TO-CELL COMMUNICATION Cells communicate with each other by sending signaling molecules to each other. The cell that synthesizes and releases the chemical is the signaling cell and the intended receiver cell is the target cell. In order to receive the signal, the target cell must have a receptor molecule to which the signaling molecule can bind. Signaling molecules can be neurotransmitters (released into synaptic clefts) and hormones. Hormones are of three types: endocrine, which use the bloodstream to be delivered to their target cells; paracrine, which is released into the extracellular space to a target cell in the near vicinity; and autocrine, which is released into the extracellular space to activate the signaling cell itself. The two major types of signaling molecules are: ○ Lipid-soluble signaling molecules or small nonpolar molecules ( e.g., NO) that penetrate the cell membrane and bind to receptors within the cytoplasm or inside the nucleus, activating intracellular messengers. Examples include hormones that influence gene transcription. ○ Hydrophilic signaling molecules bind to and activate cell surface receptors (as do some lipid- soluble signaling molecules) and have diverse physiologic effects. Examples include neurotransmitters and numerous hormones (e.g., serotonin, thyroid-stimulating hormone, insulin). Membrane Receptors Membrane receptors are primarily integral membrane glycoproteins. They are embedded in the phospholipid bilayer and have three domains, an extracellular domain that protrudes into the extracellular space and has binding sites for the signaling molecule, a transmembrane domain that passes through the phospholipid bilayer, and an intracellular domain that is located on the cytoplasmic aspect of the phospholipid bilayer and contacts either peripheral proteins or cellular organelles, thereby transducingthe extracellular contact into an intracellular event. Membrane receptor functions Control plasmalemma permeability by regulating the conformation ofion channel proteins. Regulation of the entry of molecules into the cell. Binding extracellular matrix molecules to the cytoskeleton via integrins. Act as transducers to translate extracellular events into an intracellular response via second messenger systems. Membrane receptor types Channel-linked receptors bind a signaling molecule that temporarily opens or closes the gate, permitting or inhibiting the movement of ions across the cell membrane. Examples include nicotinic acetylcholine receptors on the muscle cell sarcolemma at the myoneural junction. Catalytic receptors, also known as enzyme-linked receptors, are a type of cell-surface receptor that, upon binding to a ligand (usually a hormone or growth factor), trigger an intracellular enzymatic activity as part of the signaling process. Some catalytic receptors lack an extracytoplasmic moiety and, as a result, are continuously activated; such defective receptors are coded for by some oncogenes.  G protein-linked receptors are transmembrane proteins associated with an ion channel or with an enzyme that is bound to the cytoplasmic surface of the cell membrane. These receptors interact with heterotrimeric G protein (guanosine triphosphate [GTP]-binding regulatory protein) after binding of a signaling molecule. The heterotrimeric G protein is composed of three subunits: α, β, and γ complex. The binding of the signaling molecule causes either: (a) The dissociation of the α-subunit from the β and γ complex where the α-subunit interacts with its target or (b) The three subunits do not dissociate, but either the α-subunit and/or the β and γ complex become activated and can interact with their targets. This interaction results in the activation of intracellular second messengers, the most common of which are cyclic adenosine monophosphate (cAMP), Ca2+, and the inositol phospholipid signaling pathway.  Examples include the following: Heterotrimeric G proteins are folded so that they make seven passes as they penetrate the cell membrane. These are stimulatory Gs protein; inhibitory G protein (Gi); phospholipase C activator G protein (Gq); olfactory-specific G protein (Golf); transducin (Gt); G0 which acts to open K+ channels and close Ca2+ channels; and G12/13, which controls the formation of the actin component of the cytoskeleton and facilitates migration of the cell. Monomeric G proteins (low-molecular-weight G proteins) are small single- chain proteins that also function in signal transduction. 1. Various subtypes resemble Ras, Rho, Rab, and adenosine diphosphate (ADP) ribosylation factor (ARF) proteins. 2. These proteins are involved in pathways that regulate cell proliferation and differentiation, protein synthesis, attachment of cells to the extracellular matrix, exocytosis, and vesicular traffic.