The Cell: Cell Membrane

Characteristics and Structure

Definition

Cell membrane (also known as plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products membrane or plasmalemma) is a biological membrane that separates the contents of the cell from the outside environment.

Functions

• Barrier that protects the contents of the cell from the extracellular environment
• Anchors the cytoskeleton Cytoskeleton The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. The Cell: Cytosol and Cytoskeleton and defines cellular shape
• Attaches to the extracellular matrix Extracellular matrix A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. Hypertrophic and Keloid Scars and aids AIDS Chronic HIV infection and depletion of CD4 cells eventually results in acquired immunodeficiency syndrome (AIDS), which can be diagnosed by the presence of certain opportunistic diseases called AIDS-defining conditions. These conditions include a wide spectrum of bacterial, viral, fungal, and parasitic infections as well as several malignancies and generalized conditions. HIV Infection and AIDS in tissue formation
• Transports materials inside and outside of the cell
• Enables cellular communication Communication The exchange or transmission of ideas, attitudes, or beliefs between individuals or groups. Decision-making Capacity and Legal Competence

Composition

The composition of the cell membrane can change depending on the environment and the stage of cell development. By weight, it is composed of approximately 50% lipids Lipids Lipids are a diverse group of hydrophobic organic molecules, which include fats, oils, sterols, and waxes. Fatty Acids and Lipids and 50% proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis.

Lipids Lipids Lipids are a diverse group of hydrophobic organic molecules, which include fats, oils, sterols, and waxes. Fatty Acids and Lipids:

• Phospholipids Phospholipids Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. Lipid Metabolism (> 50% of membrane lipids Lipids Lipids are a diverse group of hydrophobic organic molecules, which include fats, oils, sterols, and waxes. Fatty Acids and Lipids):
  • Amphipathic lipids Lipids Lipids are a diverse group of hydrophobic organic molecules, which include fats, oils, sterols, and waxes. Fatty Acids and Lipids with a phosphate Phosphate Inorganic salts of phosphoric acid. Electrolytes head (polar) and 2 fatty-acid tails (nonpolar)
  • Form a double layer (lipid bilayer) with the polar heads facing the water and nonpolar ends facing each other (hydrophobic exclusion)
  • The proportion of saturated versus unsaturated fatty acids Unsaturated fatty acids Fatty acids in which the carbon chain contains one or more double or triple carbon-carbon bonds. Fatty Acids and Lipids determines membrane fluidity.
• Glycolipids (approximately 2%): 
  • Lipid attached to carbohydrate, outward-facing
  • Play a role in cell-cell interactions
  • Determine ABO blood type
  • Participate in glycocalyx formation
  • Inflammatory response
  • Viral recognition of host cells
• Cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism:
  • Amphipathic lipid with a sterol Sterol Steroids with a hydroxyl group at c-3 and most of the skeleton of cholestane. Additional carbon atoms may be present in the side chain. Mycoplasma ring
  • Hydroxyl group interacts with water
  • Sterol Sterol Steroids with a hydroxyl group at c-3 and most of the skeleton of cholestane. Additional carbon atoms may be present in the side chain. Mycoplasma ring embedded in the membrane
  • Decreases membrane fluidity
  • Increases the phase-transition range of temperature
  • Maintains membrane integrity without the need of a cell wall Cell wall The outermost layer of a cell in most plants; bacteria; fungi; and algae. The cell wall is usually a rigid structure that lies external to the cell membrane, and provides a protective barrier against physical or chemical agents. Cell Types: Eukaryotic versus Prokaryotic
  • Can also be packaged in lipoproteins Lipoproteins Lipid-protein complexes involved in the transportation and metabolism of lipids in the body. They are spherical particles consisting of a hydrophobic core of triglycerides and cholesterol esters surrounded by a layer of hydrophilic free cholesterol; phospholipids; and apolipoproteins. Lipoproteins are classified by their varying buoyant density and sizes. Lipid Metabolism for transport through the bloodstream

Proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis:

• Integral membrane proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis: 
  • Embedded in the bilayer, usually span the entire membrane (transmembrane)
  • Penetrate the membrane to transport substances
  • Examples:
    • Ion channels
    • Proton pumps
    • G-protein coupled receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors
• Peripheral proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis:
  • Reversibly attached to the membrane or integral proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis
  • Partially penetrate the membrane
  • Cell signaling and protein-protein interactions
  • Glycosylphosphatidylinositol (GPI)-linked proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis
  • The cytoskeletal proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis, ankyrin and spectrin, link to actin Actin Filamentous proteins that are the main constituent of the thin filaments of muscle fibers. The filaments (known also as filamentous or f-actin) can be dissociated into their globular subunits; each subunit is composed of a single polypeptide 375 amino acids long. This is known as globular or g-actin. In conjunction with myosins, actin is responsible for the contraction and relaxation of muscle. Skeletal Muscle Contraction.
• Lipid-anchored proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis: 
  • Attached to lipids Lipids Lipids are a diverse group of hydrophobic organic molecules, which include fats, oils, sterols, and waxes. Fatty Acids and Lipids that insert into the membrane
  • Not an integral part of the membrane
  • Example: G-proteins

Properties

• Asymmetric: The inner and outer layers have different phospholipids Phospholipids Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. Lipid Metabolism.
• Non-uniform: has domains (e.g., lipid raft)
• Concept of “fluid mosaic”: Lipid bilayer allows free lateral movement of proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis and lipids Lipids Lipids are a diverse group of hydrophobic organic molecules, which include fats, oils, sterols, and waxes. Fatty Acids and Lipids.
• Transition temperature (10°C–40°C):
  • At low temperatures, the membrane changes to a gel-like solid state.
  • The membrane loses fluidity (becomes more rigid).
  • Cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism helps preserve membrane fluidity at low temperatures.
• Selective permeability:
  • Permeable to:
    • Gases (e.g., CO₂, CO, O₂)
    • Small uncharged polar molecules (e.g., H₂O, ethanol Ethanol A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. Ethanol Metabolism, urea Urea A compound formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. Urea Cycle)
  • Not permeable to:
    • Large uncharged polar molecules (e.g., glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance)
    • Ions (e.g., Na⁺, K⁺)
    • Charged polar molecules (e.g., ATP, amino acids Amino acids Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. Basics of Amino Acids)

Membrane Transport

Transmembrane gradients

• Concentration gradient of certain ions:
  • Na⁺ concentration is higher outside the cell.
  • K⁺ concentration is higher inside the cell.
• Membrane potential Membrane potential The membrane potential is the difference in electric charge between the interior and the exterior of a cell. All living cells maintain a potential difference across the membrane thanks to the insulating properties of their plasma membranes (PMs) and the selective transport of ions across this membrane by transporters. Membrane Potential: 
  • Electrical gradient across membrane
  • Inside of the cell is more negative than the outside.
• Electrochemical gradient: 
  • Maintained by the Na⁺/K⁺ pump Pump ACES and RUSH: Resuscitation Ultrasound Protocols: a transmembrane protein structure that hydrolyzes ATP and transports 3 Na⁺ ions out of the cell for every 2 K⁺ ions moved into the cell
  • Generates a combination of electrical and concentration gradients: 
    • Na⁺ moves into the cell based on both concentration and electrical gradients.
    • K⁺ moves into the cell based on electrical gradient Electrical gradient Renal Potassium Regulation and moves out of the cell based on concentration gradient.

Transport proteins Transport proteins Proteins and Peptides

• Channels: 
  • Open to the environment on both sides simultaneously
  • Ion channel proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis
  • Bring about a considerable change in ion concentration by opening/closing
  • Participate in facilitated diffusion Diffusion The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space. Diffusion, especially facilitated diffusion, is a major mechanism of biological transport. Peritoneal Dialysis and Hemodialysis of ions
• Carriers: 
  • Only 1 side (gate) opens at a time
  • Presence of binding sites that recognize specific molecules
  • Recognize specific molecules
  • Membrane-transport carrier Carrier Vaccination proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis that transfer 2 or more molecules across the membrane are called cotransporters:
    • Symporter: 2 solutes moved in the same direction 
    • Antiporter: 2 solutes moved in the opposite directions

Membrane transport

• Passive transport (facilitated diffusion Diffusion The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space. Diffusion, especially facilitated diffusion, is a major mechanism of biological transport. Peritoneal Dialysis and Hemodialysis) moves substances from high concentration to low concentration (down the concentration gradient):
  • Does not require energy input
  • The channels open and allow molecules to diffuse into the cell until concentrations equalize.
  • Ion channels are “ion-specific”  (e.g., Na⁺ channel allows diffusion Diffusion The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space. Diffusion, especially facilitated diffusion, is a major mechanism of biological transport. Peritoneal Dialysis and Hemodialysis only of Na⁺)
• Active transport moves substances from low concentration to high concentration (against the concentration gradient):
  • Requires carrier Carrier Vaccination protein to bind BIND Hyperbilirubinemia of the Newborn substrate Substrate A substance upon which the enzyme acts. Basics of Enzymes
  • Primary active transport requires energy (usually ATP).
  • Secondary active transport: 
    • Uses electrochemical gradient generated by primary active transport
    • Cotransporters move a molecule toward a gradient while simultaneously moving another molecule against the gradient.
    • Na⁺/ Ca CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts)²⁺ pump Pump ACES and RUSH: Resuscitation Ultrasound Protocols: uses Na⁺ influx to move Ca CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts)²⁺ out of the cell
• Endocytosis: engulfing of particles or ions by the formation of membrane vesicles Vesicles Female Genitourinary Examination that pinch off from plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products membrane
• Exocytosis: excretion of certain substances by fusion of membrane vesicles Vesicles Female Genitourinary Examination with the outer membrane of the cell

Clinical Relevance

Disorders of the plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products membrane

• Hereditary spherocytosis Hereditary Spherocytosis Hereditary spherocytosis (HS) is the most common type of hereditary hemolytic anemia. The condition is caused by a cytoskeletal protein deficiency in the RBC membrane. This results in loss of membrane stability and deformability of the RBC, giving the cell its spherical shape (spherocyte). Hereditary Spherocytosis: an autosomal-dominant inherited disease of the RBCs RBCs Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology, which presents as a morphological change of the erythrocytes Erythrocytes Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology to the so-called spherocytes. Changes in the shape of the plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products membrane are associated with mutations in the cytoskeletal proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis. Defective spherocytes are cleared from the circulation Circulation The movement of the blood as it is pumped through the cardiovascular system. ABCDE Assessment by the spleen Spleen The spleen is the largest lymphoid organ in the body, located in the LUQ of the abdomen, superior to the left kidney and posterior to the stomach at the level of the 9th-11th ribs just below the diaphragm. The spleen is highly vascular and acts as an important blood filter, cleansing the blood of pathogens and damaged erythrocytes. Spleen: Anatomy leading to anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types. Treatment is with folic acid and, when necessary, a splenectomy Splenectomy Surgical procedure involving either partial or entire removal of the spleen. Rupture of the Spleen. 
• Paroxysmal nocturnal hemoglobinuria Hemoglobinuria The presence of free hemoglobin in the urine, indicating hemolysis of erythrocytes within the vascular system. After saturating the hemoglobin-binding proteins (haptoglobins), free hemoglobin begins to appear in the urine. Transfusion Reactions: a rare and serious acquired chronic hemolytic anemia Chronic Hemolytic Anemia Anemia: Overview and Types with periodic exacerbations caused by a defect in the PIGA gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics. PIGA genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure are responsible for the 1st step in the synthesis Synthesis Polymerase Chain Reaction (PCR) of the GPI anchor that attaches a subset of proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis to the cell surface. The most important of these cell-surface proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis are CD59 and CD55, which protect the cell from complement-mediated cell lysis.

Pharmacology

• Ion-channel blockers: 
  • Neurotoxic alkaloids from pufferfish and shellfish block the Na⁺ channels of neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology.
  • Cardiac arrhythmias are treated using K⁺ and Na⁺ blockers.
  • Antihypertensive drugs block Na⁺ channels.
• Ion-channel openers:
  • Vasodilators Vasodilators Drugs used to cause dilation of the blood vessels. Thromboangiitis Obliterans (Buerger’s Disease) such as minoxidil, diazoxide, and nicorandil open K⁺ channels.
  • Anticonvulsants such as retigabine and flupirtine open specific K⁺ channels.
  • Benzodiazepines Benzodiazepines Benzodiazepines work on the gamma-aminobutyric acid type A (GABAA) receptor to produce inhibitory effects on the CNS. Benzodiazepines do not mimic GABA, the main inhibitory neurotransmitter in humans, but instead potentiate GABA activity. Benzodiazepines and barbiturates Barbiturates A class of chemicals derived from barbituric acid or thiobarbituric acid. Many of these are gaba modulators used as hypnotics and sedatives, as anesthetics, or as anticonvulsants. Intravenous Anesthetics potentiate gamma-aminobutyric acid ( GABA GABA The most common inhibitory neurotransmitter in the central nervous system. Receptors and Neurotransmitters of the CNS) receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors, which are Cl^– ion channels.
• Ionophores (lipid carriers of ions across membranes):
  • K⁺ ionophores: 
    • Antibiotics that bind BIND Hyperbilirubinemia of the Newborn to the bacterial cell and disrupt K⁺ gradient
    • For example, valinomycin, nystatin Nystatin Macrolide antifungal antibiotic complex produced by streptomyces noursei, s. Aureus, and other streptomyces species. The biologically active components of the complex are nystatin a1, a2, and a3. Polyenes, salinomycin
  • Proton ionophores (2,4-dinitrophenol):
    • Allow protons to leak across the mitochondrial membrane
    • Disrupt ATP synthesis Synthesis Polymerase Chain Reaction (PCR)
    • Highly lethal