Chapter 8. Cell Membranes

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1 Chapter 8 Cell Membranes

2 Composition of cell membrane: the fluid mosaic model 流體鑲嵌模型 ---structural element (lipid脂質) Page carry out the specific functions (protein蛋白質)

3 Phospholipids 磷脂質 Are the most abundant lipid in the plasma membrane Are amphipathic, containing both hydrophobic and hydrophilic regions Page 197 親水性 Hydrophilic head Hydrophobic tail 疏水性 WATER WATER

4 The Fluidity of Membranes Page Movement of phospholipids in the plasma membrane Lateral movement (~10 7 times per second) Flip-flop (~ once per month) Flippase in ER

5 Page 198 *Three types of phospholipid movement (rapid; distance ~ 2 m / sec) (rare) Phospholipid translocator (flippase)

6 2.Composition of hydrocarbon tails in phospholipids Page 198 Fluid Viscous Unsaturated hydrocarbon tails with kinks Saturated hydro- Carbon tails

7 Page 198

8 3.Cholesterol 膽固醇 Page 198 Has different effects on membrane fluidity at different temperatures Cholesterol

9 Page 198

10 Demonstration of the Mobility of Membrane Protein --Cell Fusion Page 198 Membrane proteins + Mouse cell Human cell Hybrid cell Mixed proteins after 1 hour

11 Evolution of Differences in Membrane Lipid Composition Page 199 Variations in lipid composition of cell membranes of many species appear to be adaptations to specific environmental conditions Ability to change the lipid compositions in response to temperature changes has evolved in organisms that live where temperatures vary

12 Membrane Proteins Page 197 Page 128

13 Integral proteins 整合膜蛋白 Penetrate the hydrophobic core of the lipid bilayer Are often transmembrane proteins, completely spanning the membrane The hydrophobic regions of an integral protein consist of one or more stretches of nonpolar amino acids, often coiled into alpha helices Peripheral proteins 周邊膜蛋白 Are bound to the surface of the membrane Page 199

14 Page 199 N-terminus EXTRACELLULAR SIDE C-terminus Helix CYTOPLASMIC SIDE

15 Page 199

16 An Overview of Six Major Functions of Membrane Proteins (a) Transport. (left) A protein that spans the membrane may provide a hydrophilic channel across the membrane that is selective for a particular solute. (right) Other transport proteins shuttle a substance from one side to the other by changing shape. Some of these proteins hydrolyze ATP as an energy source to actively pump substances across the membrane. Channel protein Carrier protein ATP Page 200 (b) Enzymatic activity. A protein built into the membrane may be an enzyme with its active site exposed to substances in the adjacent solution. In some cases, several enzymes in a membrane are organized as a team that carries out sequential steps of a metabolic pathway. Enzymes (c) Signal transduction. A membrane protein may have a binding site with a specific shape that fits the shape of a chemical messenger, such as a hormone. The external messenger (signal) may cause a conformational change in the protein (receptor) that relays the message to the inside of the cell. Signal Receptor

17 (d) Cell-cell recognition. Some glyco-proteins serve as identification tags that are specifically recognized by other cells. Page 200 Glycoprotein (e) Intercellular joining. Membrane proteins of adjacent cells may hook together in various kinds of junctions, such as gap junctions or tight junctions (see Figure 6.31). (f) Attachment to the cytoskeleton and extracellular matrix (ECM). Microfilaments or other elements of the cytoskeleton may be bonded to membrane proteins, a function that helps maintain cell shape and stabilizes the location of certain membrane proteins. Proteins that adhere to the ECM can coordinate extracellular and intracellular changes (see Figure 6.29). e.g. integrin

18 Cell-surface Proteins Are Important in the Medical Field Page 200 HIV Receptor (CD4) Co-receptor (CCR5) Receptor (CD4) but no CCR5 Plasma membrane HIV can infect a cell that has CCR5 on its surface, as in most people. HIV cannot infect a cell lacking CCR5 on its surface, as in resistant individuals.

19 The Role of Membrane Carbohydrates in Cell-Cell Recognition Page 201 Cells recognize each other by binding to molecules, often containing carbohydrates, on the extracellular surface of the plasma membrane Membrane carbohydrates may be covalently bonded to lipids (forming glycolipids) or more commonly to proteins (forming glycoproteins) Carbohydrates on the external side of the plasma membrane vary among species, individuals, and even cell types in an individual *glycolipid 醣脂質 *glycoprotein 醣蛋白

20 Synthesis and Sidedness of Membranes Lipid bilayer Page 201 Transmembrane glycoproteins Attached carbohydrate Secretory protein Golgi apparatus Vesicle Glycolipid ER lumen Plasma membrane: Cytoplasmic face Extracellular face Transmembrane glycoprotein Secreted protein Membrane glycolipid

21 Membrane Transport

22 Page 202

23 Page 203

24 Membrane transport Small molecules Passive transport 被動運輸 Active transport 主動運輸 Simple diffusion 簡單擴散 Facilitated diffusion 便捷擴散 pumps cotransporter Carrier proteins Channel proteins 載體蛋白通道蛋白 Large molecules exocytosis endocytosis

25 Transport of Small Molecules: 1. Passive transport (1)simple diffusion (passive diffusion) e. g. oxygen,carbon dioxide and ethanol (2)osmosis (water diffusion) (3)facilitated diffusion (protein-mediated movement) ---carrier protein ---channel protein 2. Active transport

26 Osmosis 滲透 Page 203

27 (a) Animal cell. An animal cell fares best in an isotonic environment unless it has special adaptations to offset the osmotic uptake or loss of water. 低張溶液 等張溶液 Page 204 高張溶液 Hypotonic solution Isotonic solution Hypertonic solution H 2 O H 2 O H 2 O H 2 O Lysed Normal Shriveled (b) Plant cell. Plant cells are turgid (firm) and generally healthiest in a hypotonic environment, where the uptake of water is eventually balanced by the elastic wall pushing back on the cell. H H 2 O H 2 O H 2 O 2 O Turgid (normal) Flaccid Plasmolyzed

28 Page 204 Hypertonic or hypotonic environments create osmotic problems for organisms that have cells without rigid walls Osmoregulation, the control of solute concentrations and water balance, is a necessary adaptation for life in such environments For example, the unicellular eukaryote Paramecium, which is hypertonic to its pond water environment, has a contractile vacuole that acts as a pump

29 Page 204 Bacteria and archaea ( 古細菌 ) that live in hypersaline (excessively salty) environments have cellular mechanisms to balance internal and external solute concentrations

30 Page 205

31 Facilitated Diffusion: Passive Transport Aided by Proteins Page 205 In facilitated diffusion, transport proteins speed the passive movement of molecules across the plasma membrane Transport proteins include channel proteins and carrier proteins

32 Page 205 Channel proteins provide corridors that allow a specific molecule or ion to cross the membrane Aquaporins facilitate the diffusion of water Ion channels facilitate the transport of ions Some ion channels, called gated channels, open or close in response to a stimulus For example, in nerve cells, ion channels open in response to electrical stimulus

33 Two Types of Transport Proteins That Carry Out Facilitated Diffusion Page 205 EXTRACELLULAR FLUID Channel protein Solute CYTOPLASM (a) A channel protein (purple) has a channel through which water molecules or a specific solute can pass. Carrier protein Solute (b) A carrier protein alternates between two conformations, moving a solute across the membrane as the shape of the protein changes. The protein can transport the solute in either direction, with the net movement being down the concentration gradient of the solute.

34 Channel proteins: 1.ion channels 2.porins 3.aquaporins Page 205 hydrophobic hydrophilic

35 1.Ion channel --- rapid ---selective ---most ion channels are not permanently open Gated channel Page 205

36 2.Porins: found in outer membranes of mitochondria, chloroplasts and many Gram negative bacteria. hydrophobic hydrophilic ( barrel) -sheet

37

38 3. Aquaporins (Channel Protein): Page water channels ---facilitate the massive amounts of diffusion -helix

39 Page 202

40 Membrane transport Small molecules Passive transport 被動運輸 Active transport 主動運輸 Simple diffusion 簡單擴散 Facilitated diffusion 便捷擴散 pumps cotransporter Carrier proteins Channel proteins 載體蛋白通道蛋白 Large molecules exocytosis endocytosis

41 Active transport uses energy to move solutes against their gradients Page 206 Facilitated diffusion is still passive because the solute moves down its concentration gradient, and the transport requires no energy Some transport proteins, however, can move solutes against their concentration gradients

42 The Need for Energy in Active Transport Page 206 Active transport requires energy, usually in the form of ATP hydrolysis, to move substances against their concentration gradients All proteins involved in active transport are carrier proteins

43 ATPase (pump) (cotransporter)

44 Page 206 Active transport: *direct active transport (driven by ATP hydrolysis; transport proteins also called transport ATPase or ATPase pumps) *indirect active transport (driven by ion gradients) --- depend on the cotransport of two solutes one is an ion (usually Na + or H + ) that move exergonically down its electrochemical gradient, driving the concomitant transport of the second solute (such as a monosaccharide or an amino acid)

45 Page 206

46 Page 207 Active transport allows cells to maintain concentration gradients that differ from their surroundings For example, an animal cell has a much higher potassium (K + ) and a much lower sodium (Na + ) concentration compared to its surroundings This is controlled by the sodium-potassium pump, a transport protein that is energized by transfer of a phosphate group from the hydrolysis of ATP

47 P-type ATPase 1. Na + /K + pump Page 207 Animal cell

48 Na + -K + pump (keep Na + low and K + high within cell) 1 Cytoplasmic Na + binds to EXTRACELLULAR 2 Na + binding stimulates FLUID [Na the sodium-potassium + ] high [K phosphorylation by ATP. + ] low pump. Na + Na + Na + Na + Na + Page 207 Na + CYTOPLASM [Na + ] low [K + ] high P ADP ATP 6 K + is released and Na + sites are receptive again; The cycle repeats. Na + Na + Na + 3 Phosphorylation causes the protein to change its conformation, expelling Na + to the outside. K + K + P 5 Loss of the phosphate restores the protein s original conformation. K + K + 4 Extracellular K + binds to the protein, triggering release of the Phosphate set. K + K + P P i

49 Page 207 EXTRACELLULAR FLUID [Na + ] high [K + ] low Na + Na + Na + Na + Na + CYTOPLASM Na + [Na + ] low [K + ] high P ADP ATP 1 Cytoplasmic Na + binds 2 Na + binding to the sodium-potassium pump. The affinity for Na + stimulates phosphorylation by ATP. is high when the protein has this shape.

50 Page 207 Na + Na + Na + P P P i 3 Phosphorylation leads 4 The new shape has a to a change in protein high affinity for K +, which shape, reducing its affinity binds on the extracellular for Na +, which is released side and triggers release outside. of the phosphate group.

51 Page Loss of the phosphate 6 K + is released; group restores the affinity for Na + is high protein s original shape, again, and the cycle which has a lower affinity repeats. for K +.

52 Animation: Active Transport Page 207

53 Passive transport Active transport Page 207 Diffusion Facilitated diffusion ATP

54 How Ion Pumps Maintain Membrane Potential Membrane potential is the voltage across a membrane Page 207 Voltage is created by differences in the distribution of positive and negative ions across a membrane The cytoplasmic side of the membrane is negative in charge relative to the extracellular side

55 Ion Gradients Across the Plasma Membrane of a Typical Mammalian Cell Ca + =10-4 mm Ca + =2.5-5 mm

56 Resting Membrane Potential 靜止膜電位

57 Page 208 Two combined forces, collectively called the electrochemical gradient, drive the diffusion of ions across a membrane A chemical force (the ion s concentration gradient) An electrical force (the effect of the membrane potential on the ion s movement)

58 An electrogenic pump is a transport protein that generates voltage across a membrane Page 208 The sodium-potassium pump is the major electrogenic pump of animal cells The main electrogenic pump of plants, fungi, and bacteria is a proton pump, which actively transports hydrogen ions (H + ) out of the cell Electrogenic pumps help store energy that can be used for cellular work

59 Cotransport: Active Transport Driven by a Concentration Gradient Page ATP H + H + + H + Proton pump H + + Sucrose-H + cotransporter + H + Diffusion of H + H + H Sucrose

60 Cotransport: Coupled Transport by a Membrane Protein Page 208 Cotransport occurs when active transport of a solute indirectly drives transport of other substances The diffusion of an actively transported solute down its concentration gradient is coupled with the transport of a second substance against its own concentration gradient

61 Membrane transport Small molecules Passive transport 被動運輸 Active transport 主動運輸 Simple diffusion 簡單擴散 Facilitated diffusion 便捷擴散 pumps cotransporter Carrier proteins Channel proteins 載體蛋白通道蛋白 Large molecules exocytosis endocytosis

62 Bulk transport across the plasma membrane occurs by exocytosis and endocytosis Page 209 Small molecules and water enter or leave the cell through the lipid bilayer or via transport proteins Large molecules, such as polysaccharides and proteins, cross the membrane in bulk via vesicles Bulk transport requires energy

63 Exocytosis Page 209

64 Exocytosis Page 209 In exocytosis, transport vesicles migrate to the membrane, fuse with it, and release their contents outside the cell Many secretory cells use exocytosis to export their products

65 Endocytosis Page 209 In endocytosis, the cell takes in macromolecules by forming vesicles from the plasma membrane Endocytosis is a reversal of exocytosis, involving different proteins There are three types of endocytosis Phagocytosis ( cellular eating ) Pinocytosis ( cellular drinking ) Receptor-mediated endocytosis

66 Phagocytosis Pinocytosis Page 210 Receptor-Mediated Endocytosis EXTRACELLULAR FLUID Solutes Pseudopodium Solutes Plasma membrane Coat protein Receptor Food or other particle Coated pit Food vacuole Coated vesicle Coated vesicle with specific solutes (purple) bound to receptors (red) CYTOPLASM

67 Page In receptor-mediated endocytosis, binding of specific solutes to receptors triggers vesicle formation Receptor proteins, receptors, and other molecules from the extracellular fluid are transported in the vesicles Emptied receptors are recycled to the plasma membrane

68 Page Human cells use receptor-mediated endocytosis to take in cholesterol, which is carried in particles called low-density lipoproteins (LDLs) Individuals with the disease familial hypercholesterolemia have missing or defective LDL receptor proteins

69 Receptor-mediated Endocytosis : LDL (low-density lipoprotein)

70 Page 209 LDL LDL receptor Normal cell Mild disease Severe disease

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