CELL MEMBRANES (MAS)

Transcription

1 CELL MEMBRANES (MAS) 1

2 CELL MEMBRANE area of the cell immediately surrounding the cytoplasm the most conserved structure in living cells. Every living thing on this planet has some type of membrane 2

3 Anatomy of an animal cell 3

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5 Anatomy of a plant cell 5

6 CELL MEMBRANE 1. are thin structures, measuring 8 nm thick. 2. the major barrier in the cell, separating the inside of the cell from the outside. 3. It is this structure which allows cells to selectively interact with their environment 4. highly organized and asymmetric having two faces with different topologies and different functions 5. Membranes are also dynamic, constantly adapting to changing environmental conditions 6

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8 CELL MEMBRANE 6. not permeable to ionic or molecules that are non-polar. Only permeable if attached to specific proteins. 7. not rigid can modify shape and size 8. durable few months 9. trilaminar appearance 2 dark lines separated with lighter space 10. contains proteins enzyme activity 8

9 Trilaminar appearance 9

10 Membranes are vital because 1. Encloses the cell 2. defines its boundries 3. maintains essential differences between cytosol and extracellular environment 4. maintain the characteristic differences between contents of different organelles and the cytosol 5. synthesis of ATP through activities of specialized membrane proteins 10

11 Membranes are vital because 6. drive transmembrane movement of selected solutes 7. produce and transmit electrical signals nerve and muscle cells 8. acts as sensors of external signals change its behavior in response to environmental changes (transfer information, not ions) 11

12 All membranes 1. have similar chemical components 2. similar structural organization 3. similar general properties However, different membranes have 1. different specialized lipids 2. different proteins 3. different carbohydrates Physiological interactions of the different molecules are similar 12

13 How did early cell biologists deduce 1. membrane structure from electron microscopic images and 2. the knowledge that membranes were lipoprotein complexes? 13

14 All biological membranes have a common general feature a very thin film of lipid and protein molecules major components However, amounts differ depending on the types of membranes e.g. mitochondria 80% protein & 20% lipid ; myelin sheath 80% lipid & 20% protein Also contain carbohydrates - + protein = glycoprotein; + lipid = lipoprotein Universal basis for cell-membrane structure = lipid bilayer 14

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16 LIPIDS 2 main types i. phospholipid ii. sterol phosphoglycerides (glycerophospholipid) sphingolipid The distribution varies depending on the types of membranes 16

17 Phosphoglycerides The main type of phospholipid derived from glycerol-3-phosphate Simplest member = phosphatidic acid The rest are derived from it e.g. phosphatidilethanolamine from amine choline,.serine,. inositol etanolamina, choline, serine & inositol are polar 17

18 The main type of phospholipid Also known as phosphoglycerides Derived from glycerol-3- phosphate Simplest = phosphatidic acid (phosphatidate) 18

19 Phosphatidylcholine with choline as polar head group, is an example of a glycerophospholipid. It is a common membrane lipid. Phosphatidylinositol, with inositol as polar head group, is another glycerophospholipid. In addition to being a membrane lipid, phosphatidylinositol has roles in cell signaling, to be discussed later. 19

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21 Each glycerophospholipid has: 1. a polar region [glycerol, carbonyl oxygens of fatty acids, phosphate, and the polar head group (designated X above)] 2. two non-polar hydrocarbon tails of fatty acids (designated R 1, R 2 above). 21

22 SPHINGOLIPID main compound sphingosine = amino alcohol if add phosphocholine to OH group sphingomyelin various combinations serine, ethanolamine etc several types of sphingolipids most abundant = sphingomyelin 22

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24 SPHINGOMYELIN 24

25 3. CHOLESTEROL 1. Compact molecules 2. Can be found free or as an ester The cholesterol molecule inserts itself in the membrane with the same orientation as the phospholipid molecules polar head aligned with polar head of lipid 25

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27 PROTEINS 2 types 1. Peripheral (extrinsic) 2. Integral (intrinsic) 27

28 PERIPHERAL PROTEINS 1. Found on the surface of proteins exposed on both sides internal & external to cytosolic contents & external environment 2. proteins can be separated with salt concentrations Y? 30% a/acid residues are hydrophobic; 70% are hydrophilic or neutral salt solution protects electrostatic interactions 3. EDTA (chelates Mg 2+, Ca 2+ ) ; extreme ph can dissolve proteins 4. Most are enzymes with specific activities; soluble in water; free from lipid 28

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30 Peripheral protein 30

31 2. INTEGRAL PROTEINS 1. embedded in the bilayer 2. exposed to both sides of the membrane 3. involved in sending specialized substances or Messages through membrane 31

32 2. INTEGRAL PROTEINS 4. difficult to isolate necessary to use detergent or organic solvent denature protein and loss of biological activity 5. How detergent works? disrupts bilayer Detergents are amphiphatic molecules form micelles- hydrophobic ends react with hydrophobic regions of membranes dissociates the protein 32

33 Universal basis for cell-membrane structure = lipid bilayer Why? How? The bilayer is attributable to the special properties of the lipid molecules which cause them to spontaneously assemble into bilayers even in simple artificial conditions 33

34 In aqueous medium, amphiphilic molecules form micelle 1. Globular / ellipsoidal or elongated Soap and detergent 34

35 Amphiphilic One-tail (Soap) Form Spherical Or Ellipsoidal Micelle Depends On The Tail Length Hydrocarbon groups not in contact with water Head group soluble in water 35

36 Two-tail hydrocarbon (glycerophospholipid, sphingolipid) Form extended micelle - known as lipid bilayer LIPID BILAYER - FORM THE BASIC STRUCTURE OF MEMBRANE 36

37 Glycerophospholipids suspension can form liposomes - closed vesicles surrounded by a phospholipid bilayer 37

38 Phospholipid bilayer Hydrophilic group faces out towards both aqeous regions Tail group (hydrophobic) faces towards inside the layer 38

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41 At appropriate concentrations spheres = micelles tails =hydrophobic inside exclude water ; polar heads outside of sphere They can also form bimolecular sheets or bilayers with the hydrophobic tails sandwiched between the hydrophilic heads Basic structure for all membranes 41

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43 MEMBRANE STRUCTURE Historical Perspective How did early cell biologists deduce membrane structure from electron microscopic images and the knowledge that membranes were lipoprotein complexes? 43

44 In 1900 Overton Measured the permeability of various types of compounds across the membranes of a frog muscle found that lipid molecules could readily cross this membrane, larger lipid insoluble molecules couldn't and small polar compounds could slowly cross the membrane. He suggested that membranes were similar to lipids and that certain molecules (lipids) moved across membranes by dissolving in the membrane. suggest that the biologic membrane is mainly lipid in nature but contains small aqueous channels or pores. 44

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46 1930's-40's, Danielli and Davson studied triglyceride lipid bilayers over a water surface. Found that they arranged themselves with the polar heads facing outward. However, they always formed droplets (oil in water) and the surface tension was much higher than that of cells. However, if you added proteins, the surface tension was reduced and the membranes flattened out. 46

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48 The Davson-Danielli Model 48

49 Later work (Danielli, 1975) suggested the presence of "active patches" and protein lining to pores in the membrane. Modified Davson-Danielli Model 49

50 Basic structural characteristics of membranes derived from the physiological properties of the major lipids i. amphipathic 1. glycerophospholipids 2. sphingolipids ii. hydrophilic heads and hydrophobic tails iii. phospholipids tails = hydrophobic = 2 = hydrocarbon chains (12-14 C) 50

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52 PHOSPHOLIPIDS 52

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55 At appropriate concentrations spheres = micelles tails =hydrophobic inside exclude water ; polar heads outside of sphere They can also form bimolecular sheets or bilayers with the hydrophobic tails sandwiched between the hydrophilic heads Basic structure for all membranes 55

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57 Problem : How lipids and protein are combined membrane Explained by the FLUID MOSAIC MODEL model highlights the fact that: 1. the membrane is fluid phospholipids held together by hydrophobic interactions lateral movement of phospholipid is common (~2mm/sec ) fluidity increases when fatty acids are unsaturated fluidity increases with cholesterol 57

58 2. the membrane is a mosaic of macromolecules most characteristics of membrane are due to proteins Two types of proteins: 1. Integral - pierce through Carriers Gates Pores Receptors 58

59 2. Peripheral - partly submerged, sometimes linked to integral Enzymes Antibodies etc. 59

60 Evidence to support FLUID-MOSAIC model? 1. Fluid Fluorescent dye attached to membrane bleached with laser spot gradually spreads as marked molecules exchange places with unmarked molecules measure fluidity - time taken for spot to diasappear 60

61 Evidence to support FLUID-MOSAIC model? 1. Fluid 61

62 1. Fuse human and mouse cells 2. conjugate these antibodies to fluorescein (green) or rhodamine (red) fluorescent compounds 3. After 40 min at 37 C, the labels mixed and the cells showed mixing of the two dyes 62

63 MEMBRANE FLUIDITY Lipid bilayer is considered as a twodimensional fluid membrane hydrocarbon tails are "fluid" when membrane is functional The interior is in constant motion - lipids/proteins diffuse laterally demonstrating membrane fluidity Lipid tails bend - different lengths and the presence of double bonds 63

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66 Lipid movement Transverse diffusion - flip plop - seldom occurs Lateral diffusion - lipid molecules move within the plane of the bilayer Exchange of one pair of neighboring lipid molecules within the same layer Lipids in membrane can move about 1 µm length in ~ 1 s (bacteria) 66

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68 (Frequent) (Rare) 68

69 Membrane Fluidity Membrane must be fluid to be functional 1. to allow protein to collide and interact 2. to allow special lipids to carry e - and H + across membrane 69

70 There are four basic types of transport systems 1. Passive Diffusion 2. Facilitated Diffusion 3. Group Translocation 4. Active Transport 70

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72 Passive transport where molecules move from an area of high concentration to an area of low concentration without the use or input of energy by the cell, this process is known as diffusion. Diffusion is driven entirely by the kinetic energy the molecules possess. 72

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74 2. Facilitated Diffusion This involves a protein that binds the molecule to transport and is therefore specific. However, solutes are not concentrated against a gradient nor is energy required. It is not a widely used strategy in procaryotes. E.G. Liver cells - there is a transport protein which allows glucose to freely pass back and forth across the membrane. 74

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76 FACILITATED DIFFUSION 76

77 3. Active transport Transfer of a substance into or out of a cell from a region of lower concentration to a region of higher concentration by a process that requires a carrier and an expenditure of energy, usually in the form of ATP. Examples include transport of large molecules (non-lipid soluble) and the sodium-potassium pump 77

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82 FUNCTIONS OF MEMBRANES 82

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85 STEROID HORMONES Divided into 2 classes Sex and progestational hormones Adrenal hormones Synthesized from cholesterol Pass through the required intermediate, 5 - pregnenolone Structure is related to cyclopentanoperhydrophenanthrene nucleus 85

86 Perhydrocyclopentanophenanthrene nucleus 86

87 Some important mammalian steroid hormones Pregnenolone: produced directly from cholesterol, the precursor molecule for all C18, C19 and C21 steroids Progesterone: produced directly from pregnenolone and secreted from the corpus luteum, responsible for changes associated with luteal phase of the menstrual cycle, differentiation factor for mammary glands 87

88 Some important mammalian steroid hormones Aldosterone: the principal mineralocorticoid, produced from progesterone in the zona glomerulosa of adrenal cortex, raises blood pressure and fluid volume, increases Na + uptake Testosterone: an androgen, male sex hormone synthesized in the testes responsible for secondary male sex characteristics, produced from progesterone 88

89 Estradiol: Some important mammalian steroid hormones an estrogen, principal female sex hormone produced in the ovary, responsible for secondary female sex characteristics Cortisol: dominant glucocorticoid in humans- from progesterone in the zona fasciculata of the adrenal cortex stress adaptation, elevates blood pressure and Na + uptake, numerous effects on the immune system 89