1. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Dee Unglaub Silverthorn, Ph.D. H UMAN P HYSIOLOGY PowerPoint ® Lecture Slide Presentation by Dr. Howard D. Booth, Professor of Biology, Eastern Michigan University AN INTEGRATED APPROACH T H I R D E D I T I O N Chapter 5 Membrane Dynamics

2. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings About this Chapter Cell membrane structures and functions Membranes form fluid body compartments Membranes as barriers and gatekeepers How products move across membranes Distribution of water and solutes in cells & the body Chemical and electrical imbalances Membrane permeability and changes

3. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Membranous tissues: Example: pericardial membrane Epithelial tissues: one to many cells thick Cell Membranes (plasmalemma) enclose cells Membranes: two meanings Figure 5-1: Membranes in the body

4. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Cell structure & support Barrier isolates cell (impermeable) Chemically Physically Regulates exchange (semipermeable) Cell communication Cell Membranes: Overview

5. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Cell Membranes: Overview Figure 5-2: The fluid mosaic model of the membrane

6. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Phospholipid bilayer and cholesterol Membrane proteins Peripheral (associated) Integral Membrane Structure

7. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Structure Cell polarity Phosphorylation Extracellular matrix Structural Membrane Proteins: Membrane-Spanning

8. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Structural Membrane Proteins: Membrane-Spanning Figure 5-4: The cytoskeleton is anchored to the cell membrane

9. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Structural Membrane Proteins: Membrane-Spanning Figure 5-5: Membrane-spanning proteins

10. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Membrane associated enzymes External reactions Internal reactions Receptors bind specific ligand Example: Hormones Cell recognition molecules Membrane Proteins that Bind Molecules Figure 5-6: Cell membrane receptor

11. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Channel proteins Open Gated Carrier proteins Bind to substrate Slower transport Transporter Proteins: Move Products Through Membrane

12. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Transporter Proteins: Move Products Through Membrane Figure 5-7: Transport proteins of the cell membrane

13. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Transporter Proteins: Move Products Through Membrane Figure 5-9: Gating of channel proteins

14. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings The term was initially applied to the polysaccharide matrix excreted by epithelial cells forming a coating on the surface of epithelial tissuepolysaccharide Includes Glycoproteins and Glycolipids Membrane Carbohydrates: Form External Glycocalyx Figure 5-11: Map of cell membrane structure

15. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings The Glycocalyx glycocalyx — carbohydrate-rich peripheral zone of the external surface coating of the membrane in most eukaryotic cells.membranecells Description The outer surface of cells is covered with lipopolysaccharide "hairs" consisting of proteoglycans, glycoproteins and glycolipids, which are called “glycocalyx” Carbohydrate components of the glycocalyx include both compounds covalently bound to proteins or, to a lesser extent, to lipids on the cell surface, and additional glycoproteins and polysaccharides which are non-covalently attached to them. Some of the adsorbed macromolecules are components of the extracellular matrix, which makes it difficult to distinguish between such matrices and the glycocalyx with the cell membrane. Glycocalyx is considered as a protective layer on the vessel wall against pathogenic effects, a network barrier to the movement of molecules. It is assumed that the endothelial glycocalyx has a definite ultrastructure and may be connected with the cytoskeleton to serve as a mechanochemical transducer of blood flow effects (shear stress) into other processes of cell signaling.proteinslipidsmacromolecules extracellular matrix

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18. Functions of the Glycocalyx Protection: Cushions the plasma membrane and protects it from chemical injuryplasma membrane Immunity to infection: Enables the immune system to recognize and selectively attack foreign organismsimmune systemorganisms Defense against cancer: Changes in the glycocalyx of cancerous cells enable the immune system to recognize and destroy themcancerousimmune system Transplant compatibility: Forms the basis for compatibility of blood transfusions, tissue grafts, and organ transplantsblood transfusionstissue graftsorgan transplants Cell adhesion: Binds cells together so that tissues do not fall apart Inflammation regulation: Glycocalyx coating on endothelial walls in blood vessels prevents leukocytes from rolling/binding in healthy states [4]leukocytes [4] Fertilization: Enables sperm to recognize and bind to eggssperm Embryonic development: Guides embryonic cells to their destinations in the bodyembryonic cells

19. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Membrane Proteins and Functions Reviewed Figure 5-12: Map of membrane proteins

20. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Intracellular (ICF) Extracellular (ECF) Interstitial Plasma Body Fluid Compartments Figure 5-13: Body fluid compartments

21. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Energy requirements Physical requirements Overview of Movement Across Membranes Figure 5-14: Map of the ways molecules move across cell membranes

22. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Stops at equilibrium Rate factors: membrane, temperature, distance, & size Diffusion: Passive & down a concentration gradient Figure 5-16: Fick’s law of diffusion

23. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Uniport Cotransport Symport Antiport Carrier Mediated Transport: Can be Passive or Active Figure 5-17: Types of carrier-mediated transport

24. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Uses transport proteins Passive Diffusion to Equilibrium Facilitated Diffusion Figure 5- 21: Diffusion stops at equilibrium (panoramic lower left 66%)

25. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Facilitated Diffusion Figure 5-22: Diffusion of glucose into cells

26. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Uses ATP to move products Up a concentration gradient Primary Active Transport: Pumps Products Figure 5-23: The Na + - K + -ATPase

27. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Primary Active Transport: Pumps Products Figure 5-24: Mechanism of the Na + - K + -ATPase (75%)

28. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Cotransports [Ion ] restored using ATP Secondary Active Transport: Uses Kinetic Energy of [ion] Figure 5-25: Sodium-glucose symporter

29. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Cell metabolism (Chapter 4) Membrane transport (Chapter 5) Energy Transfer: Review Figure 5-26: Energy transfer in living cells

30. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Endocytosis Pathways Clathrin-mediated endocytosis is mediated by small (approx. 100 nm in diameter) vesicles that have a morphologically characteristic coat made up of a complex of proteins that are mainly associated with the cytosolic protein clathrin. Clathrin-coated vesicles (CCVs) are found in virtually all cells and form domains of the plasma membrane termed clathrin-coated pits. Coated pits can concentrate large extracellular molecules that have different receptors responsible for the receptor-mediated endocytosis of ligands, e.g. low density lipoprotein, transferrin, growth factors, antibodies and many others. Clathrin-mediated endocytosisproteinsclathrinreceptorslow density lipoproteintransferringrowth factorsantibodies Caveolae are the most common reported non-clathrin-coated plasma membrane buds, which exist on the surface of many, but not all cell types. They consist of the cholesterol-binding protein caveolin (Vip21) with a bilayer enriched in cholesterol and glycolipids. Caveolae are small (approx. 50 nm in diameter) flask-shape pits in the membrane that resemble the shape of a cave (hence the name caveolae). They can constitute up to a third of the plasma membrane area of the cells of some tissues, being especially abundant in smooth muscle, type I pneumocytes, fibroblasts, adipocytes, and endothelial cells. Uptake of extracellular molecules is also believed to be specifically mediated via receptors in caveolae. Caveolaecaveolincholesterolglycolipidssmooth musclepneumocytesfibroblastsadipocytes endothelial cells Macropinocytosis, which usually occurs from highly ruffled regions of the plasma membrane, is the invagination of the cell membrane to form a pocket, which then pinches off into the cell to form a vesicle (0.5–5 µm in diameter) filled with a large volume of extracellular fluid and molecules within it (equivalent to ~100 CCVs). The filling of the pocket occurs in a non-specific manner. The vesicle then travels into the cytosol and fuses with other vesicles such as endosomes and lysosomes. Macropinocytosiscytosolendosomeslysosomes Phagocytosis is the process by which cells bind and internalize particulate matter larger than around 0.75 µm in diameter, such as small-sized dust particles, cell debris, micro-organisms and even apoptotic cells, which only occurs in specialized cells. These processes involve the uptake of larger membrane areas than clathrin-mediated endocytosis and caveolae pathway. Phagocytosismicro-organismsapoptoticclathrin-mediated endocytosiscaveolae

31. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Transcytosis: Moves some molecules and large proteins and particles via endocytosis and exocytosis across cell membrane Phagosome: The vesicle formed via internalization, in phagocytic cells. Binds and internalizes particles > 0.75 microns Phagocytes: An Actin-mediated process. Examples, immune cells Clatherin-Mediated Endocytosis Caveolae: Non-Clatherin coated but have caveolin Vesicles in Membrane Transport

32. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Pinocytosis: non-selective Receptor mediated: specific substrate Endocytosis and Exocytosis: VacuoleTransport

33. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Endocytosis and Exocytosis: VacuoleTransport Figure 5-28: Receptor-mediated endocytosis and exocytosis

34. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings CAVEOLAE

35. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings CAVEOLAE

36. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Transcytosis Figure 5-31: Transcytosis across the capillary endothelium

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39. Cross two membranes Apical Basolateral Absorption Secretion Transepithelial Transport

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42. Transepithelial Transport Figure 5-30: Transepithelial transport of glucose

43. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings About 60% of body weight is water 67% water - intracellular 33% water - extracellular 8% plasma 25% interstitial % varies slightly with sex and age Distribution of Water and Solutes in the Body Compartments Figure 5-32: Distribution of volume in the body fluid compartments

44. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Molarity vs Molality Molarity is defined as the number of moles of solute per liter of solution. This means that if you have a 1 M solution of some compound, evaporating one liter will cause one mole of the solute to precipitate. Molality is defined as the number of moles of solute per kilogram of solvent. To make a 1 m solution, you'd take one mole of a substance and add it to 1 Kg of solvent. As a result, the final volume of a 1 m solution will be somewhat more than 1 L if the solvent is Water.

45. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Molality Molalities are more convenient than molarities in experiments that involve significant temperature changes. Because the volume of a solution increases when its temperature increases, heating makes the solutions molarity go down- but the molality, which is based on masses rather than volumes, remains unchanged.

46. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Osmolarity vs Osmolality Osmolarity is distinct from molarity because it measures moles of solute particles rather than moles of solute. The distinction arises because some compounds can dissociate in solution, whereas others cannotdissociate Plasma osmolality is affected by changes in water content. In comparison, the plasma osmolarity is slightly less than osmolality, because the total plasma weight (the divisor used for osmolality) excludes the weight of any solutes, while the total plasma volume (used for osmolarity) includes solute content. Otherwise, one liter of plasma would be equivalent to one kilogram of plasma, and plasma osmolarity and plasma osmolality would be equal. However, at low concentrations, the weight of the solute is negligible compared to the weight of the solvent, and osmolarity and osmolality are very similar.osmolaritydivisor

47. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Water freely crosses membranes Osmotic pressure (mmHg) Osmolarity Osmolality Comparing two solutions Isosmotic Hyperosmotic Hyposmotic Osmosis and Osmotic Equilibrium Figure 5-34: Osmosis and osmotic pressure

48. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Penetrating solute Non-penetrating solute Isotonic Hypertonic Hypotonic Tonicity: How a Cell Reacts in a Solution Figure 5-35a, b: Tonicity depends on the relative concentrations of nonpenetrating solutes

49. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Tonicity: How a Cell Reacts in a Solution Figure 5-35c, d: Tonicity depends on the relative concentrations of nonpenetrating solutes

50. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Separation of charged ions Membrane insulates Potential Conduction of signal Electrochemical gradient Electrical Disequilibrium

51. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Electrical Disequilibrium Figure 5-36a, b: Separation of electrical charge

52. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Resting Equilibrium Channel opening Voltage gated ATP gated (leak) Membrane Potentials: Change with Permeability

53. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Membrane Potentials: Change with Permeability Figure 5-38a, b: Potassium equilibrium potential

54. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Membrane Potentials: Change with Permeability Figure 5-38c: Potassium equilibrium potential

55. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Membrane Potentials: Change with Permeability Figure 5-39: Sodium equilibrium potential

56. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Summary Figure 5-42a: Insulin secretion and membrane transport processes

57. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Summary Figure 5-42b: Insulin secretion and membrane transport processes