Cell Membranes What does a cell need? Cell & organelle membranes • Selective isolation from environment (plasma membrane) • Energy (ATP) – [to be discussed in future lecture] • Instructions (DNA) • Machinery to carry out instructions and regulate processes (proteins) • Compartmentalization of incompatible or specialized activities (organelles) Cell Membrane Function Membrane Phospholipid Bilayer • Phospho-lipid bilayer forms the essential • Boundary between internal and external backbone of cellular membranes. environments • Selectively permeable - controls what goes in and out of cell or organelle • Attachment to extracellular surfaces or to other cells (and organelles to cytoskeleton) • Self or species recognition • Cell to cell communication • Lipid metabolism • Localization of fixed or sequential processes Synthesis of membrane lipids Synthesis of membrane lipids • Phospholipid synthesis in smooth endoplasmic reticulum • Distribution of membrane lipids from sER to other organelles – Three mechanisms Denniston & Topping, Denniston & Topping, Foundations of General, Organic, and Biochemistry Foundations of General, Organic, and Biochemistry ©2008, McGraw-Hill ©2008, McGraw-Hill Heyer 1 Cell Membranes Plasma Membrane Proteins Synthesis of membrane lipids • Phospholipid bilayer has proteins embedded in it. Types of membrane lipids: • Phospholipids – Major component of lipid bilayer • Cholesterol – Contributes to rigidity / flexibility of membrane • Sphingolipids – Two fatty acids condensed onto a serine, instead of a glycerol – Usually with longer fatty chains than on phospholipids – Polar head may be modified with a phosphate or carbohydrate (glycolipid) – Rafts of sphingolipids migrate Integral proteins: embedded into along the membrane lipid bilayer Fig. 15.10.d Peripheral proteins: attached to integral proteins Proteins can insert into lipid bilayer Transmembrane proteins • Protein domains can be hydrophobic or hydrophilic Potassium channel protein Multiple hydrophobic domains contribute to intramembrane function Functions of Plasma Plasma Membrane Proteins Membrane Proteins Provide functionality to the phospholipid barrier • Gates • Pumps • Receptors • Ligands • Anchors • Junctions • Fixed enzymes • Lipophilic enzymes Heyer 2 Cell Membranes Fluid Mosaic Model Fluid Mosaic Model of Membrane Structure of Membrane Structure – Mosaic: patchy, non-uniform distribution of proteins • Different regions or sides of the same cell may have different functions – Fluid: distribution is dynamic and changeable proteins can move laterally within membrane Membrane Carbohydrates Importing proteins to organelles – As glycoprotein or glycolipid – Added onto extracellular surface groups Membrane-enclosed organelles import proteins by one of three mechanisms. All of these processes require energy. The protein remains folded during the transport steps in mechanisms 1 and 3, but usually has to be unfolded in mechanism 2. Movement of Molecules Across Membranes Passive Transport (Diffusion) •Net movement of molecules from a region of high concentration to a region of low concentration ¸ Caused by random (Brownian) movements of molecules ¸ (Increase entropy) ¸ Each type of molecule follows its own concentration gradient ¸ At equilibrium, movement is equal in both directions Heyer 3 Cell Membranes Random molecular motion eventually results in random Factors that affect distribution (equilibrium) Rate of Diffusion • Concentration gradient – Difference in concentration between two points • Temperature (molecular movement) • Permeability of the membrane / medium • Available surface area of membrane • Distance across which diffusion must occur • Solvent state (gas > liquid > semisolid) Gradient Equilibrium FICK’S LAW Adolf Fick, 1858 Increased exchange rate by increased surface area Fick’s law of diffusion of a gas across a fluid membrane: • Microvilli Rate of diffusion = KA(P2–P1)/D Wherein: Microvillus ß K = a temperature-dependent diffusion constant. Plasma membrane ß A = the surface area available for diffusion. Microfilaments ß (P2–P1) = The difference in concentration (partial (actin filaments) pressure) of the gas across the membrane. ß D = the distance over which diffusion must take place. Intermediate filaments 0.25 µm Figure 6.26 Simple (non-selective) diffusion Concentration across cell membranes = Number of solutes in a given volume • Examples Nonpolar solutes dissolve through – Moles per liter (molar = M) membrane – Grams per 100ml (g%) • O2 – Nanogams per milliliter (ng/ml) • CO2 – Parts per thousand (ppt) • Fat soluble hormones (steroids) • Osmolarity: • Urea the sum of all solutes in a given volume • Fat soluble vitamins – in moles per liter (Osm) • Other small, fat soluble molecules Heyer 4 Cell Membranes Relative Osmosis: simple diffusion of permeability of a the solvent (water) phospholipid Osmotic bilayer pressure • Water diffuses according to its concentration gradient • ↑Osm Æ Ø[water] Ø Osm Æ↑[water] • Osmosis can generate force (osmotic pressure) Semipermeable membrane Osmolarity & Osmotic Pressure Osmolarity & Osmotic Pressure • Osmolarity (Osm): • Osmolarity (Osm): the sum of all solutes in a given volume (moles per liter) the sum of all solutes in a given volume (moles per liter) ß 1 M glucose solution = 1 Osm • Osmotic Pressure (POsm): ß 1 M glucose/1 M fructose/1 M ribose solution = 3 Osm – Force generated by osmosis ß 1 M NaCl solution = 1 M Na+/ 1 M Cl– = 2 Osm – Measure of the tendency to take on water by osmosis • Isosmotic: two solutions with the same Osm • Isotonic: two solutions with the same POsm • Hypotonic: a solution with a lower POsm than another • Hyposmotic: a solution with a lower Osm than another – I.e., loses water to the other solution • Hyperosmotic: a solution with a higher Osm than another • Hypertonic: a solution with a higher POsm than another – I.e., takes water from the other solution • Remember: ↑Osm Æ Ø[water] Ø Osm Æ↑[water] • For an isosmotic solution to be isotonic, the membrane must be equally permeable (or equally impermeable) to all solutes – All isotonic solutions are isosmotic. – But not all isosmotic solutions are isotonic. Osmosis and Water Balance Osmosis and Water Balance Prediction? ↑Osm-Ø[water] 0.05 Osm 0.03 Osm water Hypotonic to “cell” ØOsm-↑[water] Heyer 5 Cell Membranes Osmotic Swelling Selective permeability • Mechanisms to resist excessive • Except for water and small nonpolar swelling in hypotonic environments solutes, permeability of cell membranes is selective and regulated. • Permeability determined by transporter proteins. – Channels and carriers are solute specific – If no transporter, than that solute cannot cross membrane • (Artificial membranes are only semipermeable —i.e., only discriminate based upon molecular size.) Types of cellular transport • Passive transport: driven by Brownian motion Carrier mediated transport – Simple diffusion & osmosis • Transporters are binding proteins – Facilitated diffusion (carrier mediated passive transport) \ subject to • Active transport: requires chemical energy (ATP) – Specificity Saturation: – Carrier mediated when all available transporter proteins are in use – Can transport against – Competition concentration gradient – Saturation Facilitated Diffusion Facilitated Diffusion • Carrier-mediated passive transport—“gates” & “channels” Glucose channel • May be gated – Most tissues – Opens in response to insulin • Or ungated – Brain tissue • Movement from high to low concentration, only when gate is open • Gate may open/close in response to – Chemical signal – Cell voltage – Mechanical distortion Heyer 6 Cell Membranes Facilitated Diffusion Osmosis may be both simple and facilitated Aquaporins (water channels) speed water movement. • Multidrug Transporter Mechanism Active Transport Active Transport • Carrier mediated 1. Solute binds to carrier – “pumps” protein 2. Binding triggers ATP • Active: requires ATP hydrolysis, transfers • Can force movement phosphate to carrier against concentration 3. Phosphorylation gradient produces change in • Creates concentration shape of carrier gradient 4. Change in shape causes • (creates order/ carrier to move solute decreases entropy) Difference in concentration is maintained Difference in concentration is maintained by selective permeability of membrane by selective permeability of membrane • Cytosol relatively high in K+, protein, organic-phosphates • Cytosol relatively high in K+, protein, organic-phosphates • Low in Na+, Ca++, Cl– • Low in Na+, Ca++, Cl– EXTRACELLULAR Plasma FLUID membrane Ca2+ ATP pump Mitochondrion Nucleus CYTOSOL Ca2+ pump Endoplasmic ATP Ca2+ reticulum (ER) pump Key High [Ca2+ ] Low [Ca2+ ] Figure 11.11 Heyer 7 Cell Membranes Some carriers can transport two different Na+/K+ ATPase: types of solutes simultaneously very important active transporter • Antiport – Pumps 3 Na+ out per each ATP used – Pumps 2 K+ in } • Na+/K+ ATPase used to: – Maintain ion gradients – Create electrical potential (inside of cell negatively charged relative to outside). Symport: Antiport: same direction different directions + + How Na /K ATPase works Cells as Electrical Batteries e. K+ is released a. Na+ binds • Electrogenic pumps: Active transport fi chemical gradients of ions fi electrical gradients. • Electrical gradient produces a membrane potential. d. K+ binds b. ATPase • Inside of the cell is changes negative relative to the shape outside of the cell. c. Na+ is released Cells as Electrical Batteries Cotransport, or secondary active Electrogenic pumps: transport • In animal cells, primarily