1. Cell Membranes and Signaling 5

2. Chapter 5 Cell Membranes and Signaling Key Concepts 5.1 Biological Membranes Have a Common Structure and Are Fluid 5.2 Some Substances Can Cross the Membrane by Diffusion 5.3 Some Substances Require Energy to Cross the Membrane

3. Chapter 5 Cell Membranes and Signaling 5.4 Large Molecules Cross the Membrane via Vesicles 5.5 The Membrane Plays a Key Role in a Cell’s Response to Environmental Signals 5.6 Signal Transduction Allows the Cell to Respond to Its Environment

4. Concept 5.1 Biological Membranes Have a Common Structure and Are Fluid A membrane’s structure and functions are determined by its constituents: lipids, proteins, and carbohydrates. The general structure of membranes is known as the fluid mosaic model. Phospholipids form a bilayer which is like a “lake” in which a variety of proteins “float.”

5. Figure 5.1 Membrane Molecular Structure

6. Concept 5.1 Biological Membranes Have a Common Structure and Are Fluid Lipids form the hydrophobic core of the membrane. Most lipid molecules are phospholipids with two regions: Hydrophilic regions—electrically charged “heads” that associate with water molecules Hydrophobic regions—nonpolar fatty acid “tails” that do not dissolve in water

7. Concept 5.1 Biological Membranes Have a Common Structure and Are Fluid Membranes may differ in lipid composition as there are many types of phospholipids. Phospholipids may differ in: Fatty acid chain length Degree of saturation Kinds of polar groups present

8. Concept 5.1 Biological Membranes Have a Common Structure and Are Fluid Two important factors in membrane fluidity: Lipid composition—types of fatty acids can increase or decrease fluidity Temperature—membrane fluidity decreases in colder conditions

9. Concept 5.1 Biological Membranes Have a Common Structure and Are Fluid Biological membranes contain proteins, with varying ratios of phospholipids. Peripheral membrane proteins lack hydrophobic groups and are not embedded in the bilayer. Integral membrane proteins are partly embedded in the phospholipid bilayer.

10. Concept 5.1 Biological Membranes Have a Common Structure and Are Fluid Anchored membrane proteins have lipid components that anchor them in the bilayer. Proteins are asymmetrically distributed on the inner and outer membrane surfaces. A transmembrane protein extends through the bilayer on both sides, and may have different functions in its external and transmembrane domains.

11. Concept 5.1 Biological Membranes Have a Common Structure and Are Fluid Plasma membrane carbohydrates are located on the outer membrane and can serve as recognition sites. Glycolipid—a carbohydrate bonded to a lipid Glycoprotein—a carbohydrate bonded to a protein

12. Concept 5.1 Biological Membranes Have a Common Structure and Are Fluid Membranes are constantly changing by forming, transforming into other types, fusing, and breaking down. Though membranes appear similar, there are major chemical differences among the membranes of even a single cell.

13. Concept 5.2 Some Substances Can Cross the Membrane by Diffusion Biological membranes allow some substances, and not others, to pass. This is known as selective permeability. Two processes of transport: Passive transport does not require metabolic energy. Active transport requires input of metabolic energy.

14. Concept 5.2 Some Substances Can Cross the Membrane by Diffusion Passive transport of a substance can occur through two types of diffusion: Simple diffusion through the phospholipid bilayer Facilitated diffusion through channel proteins or aided by carrier proteins

15. Concept 5.2 Some Substances Can Cross the Membrane by Diffusion Diffusion is the process of random movement toward equilibrium. Speed of diffusion depends on three factors: Diameter of the molecules—smaller molecules diffuse faster Temperature of the solution—higher temperatures lead to faster diffusion

16. Concept 5.2 Some Substances Can Cross the Membrane by Diffusion Simple diffusion takes place through the phospholipid bilayer. A molecule that is hydrophobic and soluble in lipids can pass through the membrane. Polar molecules do not pass through— they are not soluble in the hydrophilic interior and form bonds instead in the aqueous environment near the membrane.

17. Concept 5.2 Some Substances Can Cross the Membrane by Diffusion Aquaporins are specific channels that allow large amounts of water (a polar molecule) to move along its concentration gradient. Water crosses membranes at a faster rate than simple diffusion. It may “hitchhike” with ions such as Na + as they pass through channels.

18. Concept 5.2 Some Substances Can Cross the Membrane by Diffusion Osmosis is the diffusion of water across membranes. It depends on the concentration of solute molecules on either side of the membrane. Water passes through special membrane channels.

19. Concept 5.2 Some Substances Can Cross the Membrane by Diffusion When comparing two solutions separated by a membrane: A hypertonic solution has a higher solute concentration. Isotonic solutions have equal solute concentrations. A hypotonic solution has a lower solute concentration.

20. Figure 5.3A Osmosis Can Modify the Shapes of Cells

21. Figure 5.3B Osmosis Can Modify the Shapes of Cells

22. Figure 5.3C Osmosis Can Modify the Shapes of Cells

23. Concept 5.2 Some Substances Can Cross the Membrane by Diffusion The concentration of solutes in the environment determines the direction of osmosis in all animal cells. In other organisms, cell walls limit the volume that can be taken up. Turgor pressure is the internal pressure against the cell wall—as it builds up, it prevents more water from entering.

24. Concept 5.2 Some Substances Can Cross the Membrane by Diffusion Diffusion may be aided by channel proteins. Channel proteins are integral membrane proteins that form channels across the membrane. Substances can also bind to carrier proteins to speed up diffusion. Both are forms of facilitated diffusion.

25. Concept 5.2 Some Substances Can Cross the Membrane by Diffusion Ion channels are a type of channel protein—most are gated, and can be opened or closed to ion passage. A gated channel opens when a stimulus causes the channel to change shape. The stimulus may be a ligand, a chemical signal.

26. Concept 5.2 Some Substances Can Cross the Membrane by Diffusion A ligand-gated channel responds to its ligand. A voltage-gated channel opens or closes in response to a change in the voltage across the membrane.

27. Figure 5.4 A Ligand-Gated Channel Protein Opens in Response to a Stimulus

28. Figure 5.6 A Carrier Protein Facilitates Diffusion (Part 1)

29. Concept 5.3 Some Substances Require Energy to Cross the Membrane Active transport requires the input of energy to move substances against their concentration gradients. Active transport is used to overcome concentration imbalances that are maintained by proteins in the membrane.

30. Concept 5.3 Some Substances Require Energy to Cross the Membrane The energy source for active transport is often ATP. Active transport is directional and moves a substance against its concentration gradient. A substance moves in the direction of the cell’s needs, usually by means of a specific carrier protein.

31. Concept 5.3 Some Substances Require Energy to Cross the Membrane Two types of active transport: Primary active transport involves hydrolysis of ATP for energy. Secondary active transport uses the energy from an ion concentration gradient, or an electrical gradient.

32. Concept 5.3 Some Substances Require Energy to Cross the Membrane The sodium–potassium (Na + –K + ) pump is an integral membrane protein that pumps Na + out of a cell and K + in. One molecule of ATP moves two K + and three Na + ions.

33. Figure 5.7 Primary Active Transport: The Sodium–Potassium Pump

34. Concept 5.3 Some Substances Require Energy to Cross the Membrane Secondary active transport uses energy that is “regained,” by letting ions move across the membrane with their concentration gradients. Secondary active transport may begin with passive diffusion of a few ions, or may involve a carrier protein that transports both a substance and ions.

35. Concept 5.4 Large Molecules Cross the Membrane via Vesicles Macromolecules are too large or too charged to pass through biological membranes and instead pass through vesicles. To take up or to secrete macromolecules, cells must use endocytosis or exocytosis.

36. Figure 5.8 Endocytosis and Exocytosis (Part 1)

37. Figure 5.8 Endocytosis and Exocytosis (Part 2)

38. Concept 5.4 Large Molecules Cross the Membrane via Vesicles Three types of endocytosis brings molecules into the cell: phagocytosis, pinocytosis, and receptor–mediated endocytosis. In all three, the membrane invaginates, or folds around the molecules and forms a vesicle. The vesicle then separates from the membrane.

39. Concept 5.4 Large Molecules Cross the Membrane via Vesicles In phagocytosis (“cellular eating”), part of the membrane engulfs a large particle or cell. A food vacuole (phagosome) forms and usually fuses with a lysosome, where contents are digested.

40. Concept 5.4 Large Molecules Cross the Membrane via Vesicles In pinocytosis (“cellular drinking”), vesicles also form. The vesicles are smaller and bring in fluids and dissolved substances, as in the endothelium near blood vessels.

41. Concept 5.4 Large Molecules Cross the Membrane via Vesicles Receptor–mediated endocytosis depends on receptors to bind to specific molecules (their ligands). The receptors are integral membrane proteins located in regions called coated pits. The cytoplasmic surface is coated by another protein (often clathrin).

42. Concept 5.4 Large Molecules Cross the Membrane via Vesicles When receptors bind to their ligands, the coated pit invaginates and forms a coated vesicle. The clathrin stabilizes the vesicle as it carries the macromolecules into the cytoplasm. Once inside, the vesicle loses its clathrin coat and the substance is digested.

43. Figure 5.9 Receptor-Mediated Endocytosis (Part 1)

44. Figure 5.9 Receptor-Mediated Endocytosis (Part 2)

45. Concept 5.4 Large Molecules Cross the Membrane via Vesicles Exocytosis moves materials out of the cell in vesicles. The vesicle membrane fuses with the plasma membrane and the contents are released into the cellular environment. Exocytosis is important in the secretion of substances made in the cell.

46. Synopsis of Cellular Transport Bozeman Biology

47. Concept 5.5 The Membrane Plays a Key Role in a Cell’s Response to Environmental Signals Cells can respond to many signals if they have a specific receptor for that signal. A signal transduction pathway is a sequence of molecular events and chemical reactions that lead to a cellular response, following the receptor’s activation by a signal.

48. Concept 5.5 The Membrane Plays a Key Role in a Cell’s Response to Environmental Signals Cells are exposed to many signals and may have different responses: Autocrine signals affect the same cells that release them. Paracrine signals diffuse to and affect nearby cells. Hormones travel to distant cells.

49. Figure 5.10 Chemical Signaling Concepts

50. Concept 5.5 The Membrane Plays a Key Role in a Cell’s Response to Environmental Signals Only cells with the necessary receptors can respond to a signal—the target cell must be able to sense it and respond to it. A signal transduction pathway involves a signal, a receptor, and a response.

51. Figure 5.11 Signal Transduction Concepts

52. Concept 5.5 The Membrane Plays a Key Role in a Cell’s Response to Environmental Signals A common mechanism of signal transduction is allosteric regulation. This involves an alteration in a protein’s shape as a result of a molecule binding to it. A signal transduction pathway may produce short or long term responses.

53. Concept 5.5 The Membrane Plays a Key Role in a Cell’s Response to Environmental Signals A signal molecule, or ligand, fits into a three-dimensional site on the receptor protein. Binding of the ligand causes the receptor to change its three-dimensional shape. The change in shape initiates a cellular response.

54. Figure 5.12 A Signal Binds to Its Receptor

55. Concept 5.5 The Membrane Plays a Key Role in a Cell’s Response to Environmental Signals Ligands are generally not metabolized further, but their binding may expose an active site on the receptor. Binding is reversible and the ligand can be released, to end stimulation. An inhibitor, or antagonist, can bind in place of the normal ligand.

56. Concept 5.5 The Membrane Plays a Key Role in a Cell’s Response to Environmental Signals Receptors can be classified by their location in the cell. This is determined by whether or not their ligand can diffuse through the membrane.

57. Concept 5.5 The Membrane Plays a Key Role in a Cell’s Response to Environmental Signals Cytoplasmic receptors have ligands, such as estrogen, that are small or nonpolar and can diffuse across the membrane. Membrane receptors have large or polar ligands, such as insulin, that cannot diffuse and must bind to a transmembrane receptor at an extracellular site.

58. Concept 5.5 The Membrane Plays a Key Role in a Cell’s Response to Environmental Signals Receptors are also classified by their activity: Ion channel receptors Protein kinase receptors G protein–linked receptors

59. Concept 5.5 The Membrane Plays a Key Role in a Cell’s Response to Environmental Signals Ion channel receptors, or gated ion channels, change their three- dimensional shape when a ligand binds. The acetylcholine receptor, a ligand- gated sodium channel, binds acetylcholine to open the channel and allow Na + to diffuse into the cell.

60. Concept 5.5 The Membrane Plays a Key Role in a Cell’s Response to Environmental Signals Protein kinase receptors change their shape when a ligand binds. The new shape exposes or activates a cytoplasmic domain that has catalytic (protein kinase) activity.(cascade phosphorylation)

61. Figure 5.13 A Protein Kinase Receptor

62. Concept 5.5 The Membrane Plays a Key Role in a Cell’s Response to Environmental Signals Protein kinases catalyze the following reaction: ATP + protein  ADP + phosphorylated protein Each protein kinase has a specific target protein, whose activity is changed when it is phosphorylated.

63. Concept 5.5 The Membrane Plays a Key Role in a Cell’s Response to Environmental Signals Ligands binding to G protein–linked receptors expose a site that can bind to a membrane protein, a G protein. The G protein is partially inserted in the lipid bilayer, and partially exposed on the cytoplasmic surface.

64. Concept 5.5 The Membrane Plays a Key Role in a Cell’s Response to Environmental Signals Many G proteins have three subunits and can bind three molecules: The receptor GDP and GTP, used for energy transfer An effector protein to cause an effect in the cell

65. Concept 5.5 The Membrane Plays a Key Role in a Cell’s Response to Environmental Signals The activated G protein–linked receptor exchanges a GDP nucleotide bound to the G protein for a higher energy GTP. The activated G protein activates the effector protein, leading to signal amplification.

66. Figure 5.14 A G Protein–Linked Receptor

67. Concept 5.6 Signal Transduction Allows the Cell to Respond to Its Environment Signal activation of a specific receptor leads to a cellular response, which is mediated by a signal transduction pathway. Signaling can initiate a cascade of protein interactions—the signal can then be amplified and distributed to cause different responses.

68. Concept 5.6 Signal Transduction Allows the Cell to Respond to Its Environment A second messenger is an intermediary between the receptor and the cascade of responses. In the fight-or-flight response, epinephrine (adrenaline) activates the liver enzyme glycogen phosphorylase. The enzyme catalyzes the breakdown of glycogen to provide quick energy.

69. Concept 5.6 Signal Transduction Allows the Cell to Respond to Its Environment Researchers found that the cytoplasmic enzyme could be activated by the membrane-bound epinephrine in broken cells, as long as all parts were present. They discovered that another molecule delivered the message from the “first messenger,” epinephrine, to the enzyme.

70. Concept 5.6 Signal Transduction Allows the Cell to Respond to Its Environment The second messenger was later discovered to be cyclic AMP (cAMP). Second messengers allow the cell to respond to a single membrane event with many events inside the cell—they distribute the signal. They amplify the signal by activating more than one enzyme target.

71. Figure 5.16 The Formation of Cyclic AMP

72. Concept 5.6 Signal Transduction Allows the Cell to Respond to Its Environment Signal transduction pathways involve multiple steps—enzymes may be either activated or inhibited by other enzymes. In liver cells, a signal cascade begins when epinephrine stimulates a G protein–mediated protein kinase pathway.

73. Concept 5.6 Signal Transduction Allows the Cell to Respond to Its Environment Epinephrine binds to its receptor and activates a G protein. cAMP is produced and activates protein kinase A—it phosphorylates two other enzymes, with opposite effects: Inhibition Activation

74. Figure 5.17 A Cascade of Reactions Leads to Altered Enzyme Activity (Part 1)

75. Figure 5.17 A Cascade of Reactions Leads to Altered Enzyme Activity (Part 2)

76. Concept 5.6 Signal Transduction Allows the Cell to Respond to Its Environment Inhibition—protein kinase A inactivates glycogen synthase through phosphorylation, and prevents glucose storage. Activation—Phosphorylase kinase is activated when phosphorylated and is part of a cascade that results in the liberation of glucose molecules.

77. Concept 5.6 Signal Transduction Allows the Cell to Respond to Its Environment Signal transduction ends after the cell responds—enzymes convert each transducer back to its inactive precursor. The balance between the regulating enzymes and the signal enzymes determines the cell’s response.

78. Figure 5.18 Signal Transduction Regulatory Mechanisms

79. Concept 5.6 Signal Transduction Allows the Cell to Respond to Its Environment Cells can alter the balance of enzymes in two ways: Synthesis or breakdown of the enzyme Activation or inhibition of the enzymes by other molecules

80. Concept 5.6 Signal Transduction Allows the Cell to Respond to Its Environment Cell functions change in response to environmental signals: Opening of ion channels Alterations in gene expression Alteration of enzyme activities