1. BIO 224 Introduction to Molecular and Cell Biology
Cell Membranes
BIO 224
Introduction to Molecular and Cell Biology

2. Cell membranes
Cell membranes separate the interior of cells from the external environment and provide for internal compartmentalization
All cell types are surrounded by a plasma membrane
Eukaryotic cells contain nuclei and cyto-plasmic organelles bound by membranes

3. Cell Membranes
All membranes have a similar structure: phospholipid bilayer with associated proteins
Phospholipids spontaneously form bilayers in solution due to amphipathic properties
The bilayer forms a stable barrier between two aqueous compartments and represents the basic structure of all biological membranes

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5. Membrane Lipids 50% of the mass of most cell membranes is lipids
Membranes of different structures or cell types may have varying levels and types of lipid content
Bacterial membranes are less complex than those of higher organisms having fewer lipid types present
Mammalian membranes contain many lipid types within their structure

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7. Membrane Lipids
Lipid bilayers act like two-dimensional fluids in which molecules may rotate and move laterally
Fluidity is critical to membranes and is determined by temperature and lipid composition
Lipids with unsaturated FAs and shorter FA chains remain fluid at lower temps
Cholesterol plays a major role in maintaining membrane fluidity due to its structure
It helps support rigidity of membrane while maintaining fluidity at lower temperatures

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10. Membrane Proteins Make up 25 to 75% of the mass of cell membranes
Membrane structure is thought of as a fluid mosaic with proteins inserted into the lipid bilayer
Phospholipids provide basic membrane structure and proteins carry out the specific functions of the membranes
Proteins interact with membranes in one of three ways

11. Integral Membrane Proteins
Embedded directly in the lipid bilayer
Most are called transmembrane proteins
Span the entire lipid bilayer with exposed portions on both sides of the membrane
Membrane spanning portions are usually α-helical areas of 20 to 25 nonpolar AAs
Another bilayer spanning structure is the β-barrel, formed when β sheets fold into a barrel-like structure
These proteins are amphipathic with hydrophilic portions exposed to the aqueous environment
The proteins may span the membrane only once, or multiple times
Most transmembrane proteins in eukaryote plasma membranes have added carbohydrate groups exposed on the cell surface

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13. Lipid-Anchored Membrane Proteins
Proteins anchored in membranes through covalent bonding with membrane lipids
Particular lipid groups anchor proteins to one of the faces of the plasma membrane
The hydrophobic portion of the lipid is embedded in the membrane and the protein is bound covalently to the lipid
The polypeptide is not inserted into the hydrophobic portion of the membrane

14. Peripheral Membrane Proteins
Attached to the membrane through interactions with integral or lipid-anchored membrane proteins, or polar head groups of the lipids
Do not interact with hydrophobic interior of lipid bilayer
May only bind transiently with membrane, as in signaling processes

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16. Transport Across Cell Membranes
Biological membranes are selectively permeable, allowing cells to control internal composition
Small uncharged molecules freely diffuse across
Large polar molecules and ions cannot freely diffuse across a lipid bilayer
These molecules may cross the membrane through transmembrane proteins acting as transporters
Two classes of membrane transport proteins: channel proteins and carrier proteins

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18. Channel Proteins
Form open pores in membranes, allowing molecules of proper size and charge to cross
Pores open and close in response to extracellular signals
When open, pores allow molecules to freely diffuse across the membrane
Ion channels allow passage of inorganic ions

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20. Carrier Proteins
Selectively bind and transport specific small molecules across
Behave like enzymes, binding molecules and undergoing conformational changes to open channels facilitating passage of molecules across the membrane to be released on the other side

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22. Transmembrane Transport
Passive transport across a membrane occurs through channels or carrier proteins in an energetically favorable direction due to concentration gradients
Active transport across a membrane occurs when molecules are transported in an energetically unfavorable direction in conjunction with hydrolysis of ATP as an energy source

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24. Plasma Membranes All cells are surrounded by a plasma membrane
The fundamental structure of the plasma membrane is the phospholipid bilayer
Proteins embedded in the bilayer carry out specific functions of the membrane
RBC plasma membrane studies provided the first evidence of lipid bilayer structure

25. Bilayer structure of the plasma membrane
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26. Plasma Membrane Phospholipids
More than half the lipid content in animal cell plasma membranes is made up primarily of four phospholipids in asymmetrical distribution
Phosphatidylcholine: glycerol phospholipid with a head group formed from choline
Phosphatidylethanolamine: glycerol phospholipid with a head group formed from ethanolamine

27. Plasma Membrane Phospholipids
Phosphatidylserine: glycerol phospholipid with a head group formed from serine
Sphingomyelin: phospholipid consisting of two hydrocarbon chains bound to a polar head group containing serine
Phosphatidylinostol is a glycerol phospholipid with a head group formed from inositol, found in minor quantities in some membranes
Plays a role in cell signaling

28. Other Plasma Membrane Lipids
Glycolipids are found in animal membranes with the carbohydrate portion exposed on the cell surface
Made of two hydrocarbon chains linked to polar head groups containing carbohydrates
Cholesterol is a major constituent of animal cell membranes, found in equivalent amounts to phospholipids

29. Lipid components of the plasma membrane
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30. Bilayer Characteristics
Membrane is impermeable to water soluble molecules
Bilayers composed of naturally occurring phospholipids are viscous fluids
Most FA of phospholipids have double bonds that produce kinks in the hydrocarbon chains
Kinks make the chains difficult to pack together and allows free movement

31. Bilayer Characteristics
Cholesterol inserts into the bilayer and helps control membrane fluidity
Plant cell membranes contain sterols to perform a similar function
Cholesterol and sphingolipids form lipid rafts that move within the membrane
Their function is not well understood but they appear to play roles in cell movement, endocytosis, and cell signaling

32. Plasma Membrane Proteins
Most plasma membranes are 50% protein and 50% lipid by weight
Peripheral membrane proteins can be dissociated from the membrane by treatment with polar reagents
Integral membrane proteins may only be removed by treatments that disrupt the bilayer

33. Fluid mosaic model of the plasma membrane
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34. Membrane Proteins
Studies of RBCs have provided information about specific proteins
Most peripheral proteins in RBCs are cytoskeletal components
Major integral proteins of RBCs are glycophorin and band 3
Function of glycopohrin is not known
Band 3 is responsible for anion transport

35. Solubilization of integral membrane proteins by detergents
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36. Freeze-fracture electron micrograph of human red blood cell membranes
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37. Integral membrane proteins of red blood cells
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38. Integral Proteins
Some transmembrane transport proteins are porins that form aqueous channels through membranes
Some integral proteins anchored to the membrane provide for cell recognition
Some integral proteins anchored to the membrane participate in cell signaling

39. Bacterial outer membranes
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40. Examples of proteins anchored in the plasma membrane by lipids and glycolipids
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41. Membrane Mobility
Proteins and phosphlipids cannot move quickly between faces of the membrane
Lateral movement through the membrane is allowed
Membrane proteins associated with the cytoskeleton or other proteins are restricted from moving
Plasma membranes of some cells are divided into functional domains

42. Mobility of membrane proteins
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43. Membrane Mobility
Functional domains of membranes restrict protein movement to the area with which they are associated
Lipid rafts inhibit free diffusion of some membrane proteins
Interaction of lipid rafts with the cytoskeleton stabilizes them

44. A polarized intestinal epithelial cell
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45. Structure of lipid rafts
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46. Glycocalyx
Carbohydrate groups of glycoproteins and glycolipids that are exposed on the membrane surface make up the glycocalyx
The glycocalyx provides protection for the cell surface
Carbohydrate groups in the glycocalyx act as cell surface markers

47. The Glycocalyx
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48. Binding of selectins to oligosaccharides
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49. Small Molecule Transport
Passive diffusion is the simplest method for molecules to cross the plasma membrane
Molecules dissolve in the bilayer to diffuse across then dissolve in the aqueous solution on the other side
No membrane proteins are needed
Molecule transport is down a concentration gradient
Passive diffusion is a nonselective process

50. Molecule Transport
Facilitated diffusion occurs along a concentration gradient or as a result of electric potential
It requires proteins to mediate transport of the molecules across the bilayer
Carrier proteins and channel proteins aid in facilitated diffusion across membranes

51. Active Transport
Active transport uses energy provided by another reaction to drive uphill transport of molecules in energetically unfavorable directions
Ion pumps are used to maintain ion gradients across membranes through active transport coupled to hydrolysis of ATP
ABC transporters convey nutrients in prokaryotes and remove toxins in eukaryotes

52. Model for operation of the Na+-K+ pump
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53. Ion gradients across the plasma membrane of a typical mammalian cell
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54. Structure of an ABC transporter
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55. Ion-Gradient Driven Active Transport
Active transport driven by ion gradients couples molecule transport in an unfavorable direction with transport of another molecule in an energetically favorable direction
Symport vs. Antiport

56. Active transport of glucose
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57. Glucose transport by intestinal epithelial cells (Part 1)
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58. Glucose transport by intestinal epithelial cells (Part 2)
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59. Glucose transport by intestinal epithelial cells (Part 3)
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60. Examples of antiport
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61. Endocytosis
Eukaryotes surround material for internalization in an area of plasma membrane that buds off internally in the process of endocytosis
Phagocytosis: cell eating
Occurs in specialized cells
Produce phagosomes and phagolysosomes
Pinocytosis: cell drinking
Receptor-mediated endocytosis is the best known form

62. Phagocytosis
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63. Examples of phagocytic cells
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64. Receptor-Mediated Endocytosis
Allows for selective uptake of specific macromolecules
Molecules bind with receptors in clathrin-coated pits
Pits bud to form clathrin-coated vesicles with the assistance of dynamin
Vesicles fuse with early endosomes where contents are sorted to their destination

65. Clathrin-coated vesicle formation (Part 1)
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66. Clathrin-coated vesicle formation (Part 2)
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67. Formation of clathrin-coated pits (Part 1)
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68. Formation of clathrin-coated pits (Part 2)
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69. Receptor-Mediated Endocytosis
Cholesterol uptake in mammals has provided understanding of receptor mediated endocytosis on the molecular level
Fluid phase endocytosis also functions via receptors, allowing nonspecific uptake of extracellular fluids
Endocytosis may also occur without the use of clathrin

70. Structure of LDL
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71. The LDL receptor
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72. Clathrin-Independent Endocytosis
Cells may use caveolae for uptake of molecules, independent of clathrin
Caveolin organizes creation of caveolae
Caveolae carry out receptor-mediated endocytosis via transmembrane receptors, but cavoelin and caveolae lipids also function as receptors for molecule uptake
Macropinocytosis may also be used to uptake fluids in a clathrin-independent manner

73. Caveolae
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74. Sorting in early endosomes
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75. Recycling of synaptic vesicles
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76. Protein sorting by transcytosis
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77. Disclaimer
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