2. Membrane Dynamics Cell membrane structures and functions –Membranes form fluid body compartments –Membranes as barriers and gatekeepers –How products move across membranes i.e., methods of transporti.e., methods of transport –Distribution of water and solutes in cells & the body –Chemical and electrical imbalances –Membrane permeability and changes

3. The Cell

4. © 2013 Pearson Education, Inc. Plasma Membrane Lipid bilayer and proteins in constantly changing fluid mosaicLipid bilayer and proteins in constantly changing fluid mosaic Plays dynamic role in cellular activityPlays dynamic role in cellular activity Separates intracellular fluid (ICF) from extracellular fluid (ECF)Separates intracellular fluid (ICF) from extracellular fluid (ECF) –Interstitial fluid (IF) = ECF that surrounds cells

5. The Cell Membrane Fluid Mosaic ModelFluid Mosaic Model –Phospholipids –Integral Proteins –Peripheral Proteins –Glycocalyx GlycoproteinsGlycoproteins –MHC GlycolipidsGlycolipids –Cholesterol

6. © 2013 Pearson Education, Inc. Figure 3.16 G proteins act as middlemen or relays between extracellular first messengers and intracellular second messengers that cause responses within the cell. Ligand (1st messenger) Receptor G protein Enzyme 2nd messenger Ligand* (1st messeng- er) binds to the receptor. The receptor changes shape and activates. Extracellular fluid Intracellular fluid * Ligands include hormones and neurotransmitters. Receptor Ligand 1 Slide 2

7. © 2013 Pearson Education, Inc. Figure 3.16 G proteins act as middlemen or relays between extracellular first messengers and intracellular second messengers that cause responses within the cell. Ligand (1st messenger) Receptor G protein Enzyme 2nd messenger Ligand* (1st messeng- er) binds to the receptor. The receptor changes shape and activates. Extracellular fluid Intracellular fluid * Ligands include hormones and neurotransmitters. Receptor Ligand 1 The activated receptor binds to a G protein and acti- vates it. The G protein changes shape (turns “on”), causing it to release GDP and bind GTP (an energy source). G protein GDP 2 Slide 3

8. © 2013 Pearson Education, Inc. Figure 3.16 G proteins act as middlemen or relays between extracellular first messengers and intracellular second messengers that cause responses within the cell. Ligand (1st messenger) Receptor G protein Enzyme 2nd messenger Ligand* (1st messeng- er) binds to the receptor. The receptor changes shape and activates. Extracellular fluid Intracellular fluid * Ligands include hormones and neurotransmitters. Receptor Ligand 1 The activated receptor binds to a G protein and acti- vates it. The G protein changes shape (turns “on”), causing it to release GDP and bind GTP (an energy source). G protein GDP Activated G protein activates (or inactivates) an effector protein by causing its shape to change. Effector protein (e.g., an enzyme) 2 3 Slide 4

9. © 2013 Pearson Education, Inc. Figure 3.16 G proteins act as middlemen or relays between extracellular first messengers and intracellular second messengers that cause responses within the cell. Ligand (1st messenger) Receptor G protein Enzyme 2nd messenger Ligand* (1st messeng- er) binds to the receptor. The receptor changes shape and activates. Extracellular fluid Intracellular fluid * Ligands include hormones and neurotransmitters. Receptor Ligand 1 The activated receptor binds to a G protein and acti- vates it. The G protein changes shape (turns “on”), causing it to release GDP and bind GTP (an energy source). G protein GDP Activated G protein activates (or inactivates) an effector protein by causing its shape to change. Effector protein (e.g., an enzyme) 2 3 Active 2nd messenger Inactive 2nd messenger Activated effector enzymes catalyze reactions that produce 2nd messengers in the cell. (Common 2nd messengers include cyclic AMP and Ca 2+.) 4 Slide 5

10. © 2013 Pearson Education, Inc. Figure 3.16 G proteins act as middlemen or relays between extracellular first messengers and intracellular second messengers that cause responses within the cell. Ligand (1st messenger) Receptor G protein Enzyme 2nd messenger Ligand* (1st messeng- er) binds to the receptor. The receptor changes shape and activates. Extracellular fluid Intracellular fluid * Ligands include hormones and neurotransmitters. Receptor Ligand 1 The activated receptor binds to a G protein and acti- vates it. The G protein changes shape (turns “on”), causing it to release GDP and bind GTP (an energy source). G protein GDP Activated G protein activates (or inactivates) an effector protein by causing its shape to change. Effector protein (e.g., an enzyme) 2 3 Active 2nd messenger Inactive 2nd messenger Activated effector enzymes catalyze reactions that produce 2nd messengers in the cell. (Common 2nd messengers include cyclic AMP and Ca 2+.) 4 Activated kinase enzymes Second messengers activate other enzymes or ion channels. Cyclic AMP typically activates protein kinase enzymes. 5 Slide 6

11. © 2013 Pearson Education, Inc. Figure 3.16 G proteins act as middlemen or relays between extracellular first messengers and intracellular second messengers that cause responses within the cell. Ligand (1st messenger) Receptor G protein Enzyme 2nd messenger Ligand* (1st messeng- er) binds to the receptor. The receptor changes shape and activates. The activated receptor binds to a G protein and acti- vates it. The G protein changes shape (turns “on”), causing it to release GDP and bind GTP (an energy source). Activated G protein activates (or inactivates) an effector protein by causing its shape to change. Effector protein (e.g., an enzyme) Extracellular fluid G protein GDP Intracellular fluid Cascade of cellular responses (The amplification effect is tremendous. Each enzyme catalyzes hundreds of reactions.) Activated kinase enzymes Active 2nd messenger Inactive 2nd messenger Activated effector enzymes catalyze reactions that produce 2nd messengers in the cell. (Common 2nd messengers include cyclic AMP and Ca 2+.) Second messengers activate other enzymes or ion channels. Cyclic AMP typically activates protein kinase enzymes. Kinase enzymes activate other enzymes. Kinase enzymes transfer phosphate groups from ATP to specific proteins and activate a series of other enzymes that trigger various metabolic and structural changes in the cell. * Ligands include hormones and neurotransmitters. Receptor Ligand 1 2 3 4 5 6 Slide 7

12. © 2013 Pearson Education, Inc. The Glycocalyx "Sugar covering" at cell surface"Sugar covering" at cell surface –Lipids and proteins with attached carbohydrates (sugar groups) Every cell type has different pattern of sugarsEvery cell type has different pattern of sugars –Specific biological markers for cell to cell recognition –Allows immune system to recognize "self" and "non self" –Cancerous cells change it continuously

13. Cell Membrane Structure: Fluid Mosaic Model Thickness ~ 8nm PLs Cholesterol Proteins: peripheral (associated) or integral

14. http://www.youtube.com/watch ?v=Qqsf_UJcfBc

15. Passive Transport = Diffusion = Diffusion 1.Simple diffusion 2.Osmosis 3.Facilitated diffusion (= mediated transport) Active Transport Always protein-mediated  Primary  Secondary  Receptor mediated transport

16. Movement across Membrane Membrane permeability varies for different molecules & cell types Two movement categories: Passive andPassive and ActiveActive depends on??

17. © 2013 Pearson Education, Inc. Passive Processes: Diffusion Collisions cause molecules to move down or with their concentration gradientCollisions cause molecules to move down or with their concentration gradient –Difference in concentration between two areas Speed influenced by molecule size and temperatureSpeed influenced by molecule size and temperature

18. © 2013 Pearson Education, Inc. PLAY Animation: Membrane Permeability Passive Processes Molecule will passively diffuse through membrane ifMolecule will passively diffuse through membrane if –It is lipid soluble, or –Small enough to pass through membrane channels, or –Assisted by carrier molecule

19. © 2013 Pearson Education, Inc. PLAY Animation: Diffusion Passive Processes: Simple Diffusion Nonpolar lipid-soluble (hydrophobic) substances diffuse directly through phospholipid bilayerNonpolar lipid-soluble (hydrophobic) substances diffuse directly through phospholipid bilayer –E.g., oxygen, carbon dioxide, fat-soluble vitamins

20. Simple Diffusion

21. http://www.youtube.com/watch ?v=s0p1ztrbXPY&feature=rela ted

22. Facilitated Diffusion Some molecules are too polar or too large to pass through the lipid bilayer.Some molecules are too polar or too large to pass through the lipid bilayer. Carrier proteins change shape after the molecules bind then envelopes the molecule and releases itCarrier proteins change shape after the molecules bind then envelopes the molecule and releases it The binding site is moved from one side of the membrane to the other by a change in the confirmation of the carrier protein.The binding site is moved from one side of the membrane to the other by a change in the confirmation of the carrier protein.

23. © 2013 Pearson Education, Inc. Carrier-Mediated Facilitated Diffusion Transmembrane integral proteins are carriersTransmembrane integral proteins are carriers Transport specific polar molecules (e.g., sugars and amino acids) too large for channelsTransport specific polar molecules (e.g., sugars and amino acids) too large for channels Binding of substrate causes shape change in carrier then passage across membraneBinding of substrate causes shape change in carrier then passage across membrane Limited by number of carriers presentLimited by number of carriers present –Carriers saturated when all engaged

24. http://highered.mcgraw- hill.com/sites/0072495855/stu dent_view0/chapter2/animatio n__how_facilitated_diffusion_ works.html

25. © 2013 Pearson Education, Inc. Passive Processes: Osmosis Water concentration varies with number of solute particles because solute particles displace water moleculesWater concentration varies with number of solute particles because solute particles displace water molecules Osmolarity - Measure of total concentration of solute particlesOsmolarity - Measure of total concentration of solute particles Water moves by osmosis until hydrostatic pressure (back pressure of water on membrane) and osmotic pressure (tendency of water to move into cell by osmosis) equalizeWater moves by osmosis until hydrostatic pressure (back pressure of water on membrane) and osmotic pressure (tendency of water to move into cell by osmosis) equalize

27. © 2013 Pearson Education, Inc. Tonicity Tonicity: Ability of solution to alter cell's water volumeTonicity: Ability of solution to alter cell's water volume –Isotonic: Solution with same non- penetrating solute concentration as cytosol –Hypertonic: Solution with higher non- penetrating solute concentration than cytosol –Hypotonic: Solution with lower non- penetrating solute concentration than cytosol

28. Tonicity Physiological term describing how cell volume changes if cell placed in the solutionPhysiological term describing how cell volume changes if cell placed in the solution Always comparative. Has no units.Always comparative. Has no units. –Isotonic sol’n = No change in cell –Hypertonic sol’n = cell shrinks –Hypotonic = cell expands Tonicity = OsmolarityTonicity = Osmolarity Number of particles in solutionNumber of particles in solution

29. © 2013 Pearson Education, Inc. Figure 3.9 The effect of solutions of varying tonicities on living red blood cells. Isotonic solutions Cells retain their normal size and shape in isotonic solutions (same solute/water concentration as inside cells; water moves in and out). Cells lose water by osmosis and shrink in a hypertonic solution (contains a higher concentration of solutes than are present inside the cells). Cells take on water by osmosis until they become bloated and burst (lyse) in a hypotonic solution (contains a lower concentration of solutes than are present inside cells). Hypertonic solutions Hypotonic solutions

30. © 2013 Pearson Education, Inc. Membrane Transport: Active Processes Two types of active processesTwo types of active processes –Active transport –Vesicular transport Both require ATP to move solutes across a living plasma membrane becauseBoth require ATP to move solutes across a living plasma membrane because –Solute too large for channels –Solute not lipid soluble –Solute not able to move down concentration gradient

31. © 2013 Pearson Education, Inc. Active Transport Requires carrier proteins (solute pumps)Requires carrier proteins (solute pumps) –Bind specifically and reversibly with substance Moves solutes against concentration gradientMoves solutes against concentration gradient –Requires energy

32. © 2013 Pearson Education, Inc. Active Transport: Two Types Primary active transportPrimary active transport –Required energy directly from ATP hydrolysis Secondary active transportSecondary active transport –Required energy indirectly from ionic gradients created by primary active transport

33. Active Transport Movement from low conc. to high conc.Movement from low conc. to high conc. ATP neededATP needed Creates state of disequilibriumCreates state of disequilibrium 1 o (direct) active transport1 o (direct) active transport –ATPases or “pumps” –Uniport and Antiport 2 o (indirect) active transport –Symport and antiport

34. © 2013 Pearson Education, Inc. Figure 3.10 Primary active transport is the process in which solutes are moved across cell membranes against electrochemical gradients using energy supplied directly by ATP. Slide 2 Extracellular fluid Na + Na + –K + pump K+K+ Cytoplasm 1 Three cytoplasmic Na + bind to pump protein. ATP-binding site

35. © 2013 Pearson Education, Inc. Figure 3.10 Primary active transport is the process in which solutes are moved across cell membranes against electrochemical gradients using energy supplied directly by ATP. Slide 3 Extracellular fluid Na + Na + –K + pump K+K+ Cytoplasm 1 Three cytoplasmic Na + bind to pump protein. 2 Na + binding promotes hydrolysis of ATP. The energy released during this reaction phosphorylates the pump. Na + bound P ATP-binding site

36. © 2013 Pearson Education, Inc. Figure 3.10 Primary active transport is the process in which solutes are moved across cell membranes against electrochemical gradients using energy supplied directly by ATP. Slide 4 Extracellular fluid Na + Na + –K + pump K+K+ Cytoplasm 1 Three cytoplasmic Na + bind to pump protein. 2 Na + binding promotes hydrolysis of ATP. The energy released during this reaction phosphorylates the pump. 3 Phosphorylation causes the pump to change shape, expelling Na + to the outside. Na + bound Na + released P P ATP-binding site

37. © 2013 Pearson Education, Inc. Figure 3.10 Primary active transport is the process in which solutes are moved across cell membranes against electrochemical gradients using energy supplied directly by ATP. Slide 5 Extracellular fluid Na + Na + –K + pump K+K+ Cytoplasm 1 Three cytoplasmic Na + bind to pump protein. 2 Na + binding promotes hydrolysis of ATP. The energy released during this reaction phosphorylates the pump. K+K+ 4 Two extracellular K + bind to pump. 3 Phosphorylation causes the pump to change shape, expelling Na + to the outside. Na + bound Na + released P P P ATP-binding site

38. © 2013 Pearson Education, Inc. Figure 3.10 Primary active transport is the process in which solutes are moved across cell membranes against electrochemical gradients using energy supplied directly by ATP. Slide 6 Extracellular fluid Na + Na + –K + pump K+K+ Cytoplasm 1 Three cytoplasmic Na + bind to pump protein. 2 Na + binding promotes hydrolysis of ATP. The energy released during this reaction phosphorylates the pump. K + bound 5 K + binding triggers release of the phosphate. The dephosphorylated pump resumes its original conformation. K+K+ 4 Two extracellular K + bind to pump. 3 Phosphorylation causes the pump to change shape, expelling Na + to the outside. Na + bound Na + released P P P PiPi ATP-binding site

39. © 2013 Pearson Education, Inc. Figure 3.10 Primary active transport is the process in which solutes are moved across cell membranes against electrochemical gradients using energy supplied directly by ATP. Slide 7 Extracellular fluid Na + Na + –K + pump K+K+ Cytoplasm 1 Three cytoplasmic Na + bind to pump protein. K + released 6 Pump protein binds ATP; releases K + to the inside, and Na + sites are ready to bind Na + again. The cycle repeats. 2 Na + binding promotes hydrolysis of ATP. The energy released during this reaction phosphorylates the pump. K + bound 5 K + binding triggers release of the phosphate. The dephosphorylated pump resumes its original conformation. K+K+ 4 Two extracellular K + bind to pump. 3 Phosphorylation causes the pump to change shape, expelling Na + to the outside. Na + bound Na + released P P P PiPi ATP-binding site

40. © 2013 Pearson Education, Inc. Figure 3.10 Primary active transport is the process in which solutes are moved across cell membranes against electrochemical gradients using energy supplied directly by ATP. PLAY A&P Flix™: Resting Membrane Potential Extracellular fluid Na + Na + –K + pump K+K+ Cytoplasm 1 Three cytoplasmic Na + bind to pump protein. K + released 6 Pump protein binds ATP; releases K + to the inside, and Na + sites are ready to bind Na + again. The cycle repeats. 2 Na + binding promotes hydrolysis of ATP. The energy released during this reaction phosphorylates the pump. K + bound 5 K + binding triggers release of the phosphate. The dephosphorylated pump resumes its original conformation. K+K+ 4 Two extracellular K + bind to pump. 3 Phosphorylation causes the pump to change shape, expelling Na + to the outside. Na + bound Na + released P P P PiPi ATP-binding site

41. http://www.youtube.com/watch?v=9CBo BewdS3U&feature=relatedhttp://www.youtube.com/watch?v=9CBo BewdS3U&feature=relatedhttp://www.youtube.com/watch?v=9CBo BewdS3U&feature=relatedhttp://www.youtube.com/watch?v=9CBo BewdS3U&feature=related

42. http://www.youtube.com/watch?v=STzO iRqzzL4&NR=1http://www.youtube.com/watch?v=STzO iRqzzL4&NR=1http://www.youtube.com/watch?v=STzO iRqzzL4&NR=1http://www.youtube.com/watch?v=STzO iRqzzL4&NR=1

43. © 2013 Pearson Education, Inc. Secondary Active Transport Depends on ion gradient created by primary active transportDepends on ion gradient created by primary active transport Energy stored in ionic gradients used indirectly to drive transport of other solutesEnergy stored in ionic gradients used indirectly to drive transport of other solutes

44. CotransportSymport Molecules are carried in same directionMolecules are carried in same direction Examples: Glucose and Na +Examples: Glucose and Na +Antiport Molecules are carried in opposite directionMolecules are carried in opposite direction Examples: Na + /K + pumpExamples: Na + /K + pump

45. © 2013 Pearson Education, Inc. Figure 3.11 Secondary active transport is driven by the concentration gradient created by primary active transport. Slide 2 Extracellular fluid Na + -K + pump Cytoplasm Primary active transport The ATP-driven Na + -K + pump stores energy by creating a steep concentration gradient for Na + entry into the cell. 1

46. © 2013 Pearson Education, Inc. Figure 3.11 Secondary active transport is driven by the concentration gradient created by primary active transport. Slide 3 Extracellular fluid Na + -glucose symport transporter loads glucose from extracellular fluid Na + -glucose symport transporter releases glucose into the cytoplasm Glucose Na + -K + pump Cytoplasm Primary active transport The ATP-driven Na + -K + pump stores energy by creating a steep concentration gradient for Na + entry into the cell. Secondary active transport As Na + diffuses back across the membrane through a membrane cotransporter protein, it drives glucose against its concentration gradient into the cell. 1 2

47. Table 5-4

48. © 2013 Pearson Education, Inc. Vesicular Transport Transport of large particles, macromolecules, and fluids across membrane in membranous sacs called vesiclesTransport of large particles, macromolecules, and fluids across membrane in membranous sacs called vesicles Requires cellular energy (e.g., ATP)Requires cellular energy (e.g., ATP)

49. © 2013 Pearson Education, Inc. Vesicular Transport Functions:Functions: –Endocytosis—transport into cell Phagocytosis, pinocytosis, receptor- mediated endocytosisPhagocytosis, pinocytosis, receptor- mediated endocytosis –Exocytosis—transport out of cell

50. Vesicular Transport Movement of macromolecules across cell membrane: 1.Phagocytosis (specialized cells only) Macrophage or Phagocytes 2.Pinocytosis “Cell drinking” 3.Receptor mediated endocytosis Down Regulation 4.Exocytosis

51. Vesicular Transport

52. © 2013 Pearson Education, Inc. Endocytosis PhagocytosisPhagocytosis –Pseudopods engulf solids and bring them into cell's interior –Form vesicle called phagosome Used by macrophages and some white blood cellsUsed by macrophages and some white blood cells –Move by amoeboid motion Cytoplasm flows into temporary extensionsCytoplasm flows into temporary extensions Allows creeping Allows creeping

53. http://www.youtube.com/watch?v=Z_m XDvZQ6dUhttp://www.youtube.com/watch?v=Z_m XDvZQ6dUhttp://www.youtube.com/watch?v=Z_m XDvZQ6dUhttp://www.youtube.com/watch?v=Z_m XDvZQ6dU

55. Endocytosis Nonselective:Nonselective: Pinocytosis for fluids & dissolved substancesPinocytosis for fluids & dissolved substances Selective:Selective: Receptor Mediated Endocytosis via clathrin- coated pits - Example: LDL cholesterol and Familial HypercholesterolemiaReceptor Mediated Endocytosis via clathrin- coated pits - Example: LDL cholesterol and Familial Hypercholesterolemia

56. © 2013 Pearson Education, Inc. Endocytosis Pinocytosis (fluid-phase endocytosis)Pinocytosis (fluid-phase endocytosis) –Plasma membrane infolds, bringing extracellular fluid and dissolved solutes inside cell Fuses with endosomeFuses with endosome –Most cells utilize to "sample" environment –Nutrient absorption in the small intestine –Membrane components recycled back to membrane

57. Pinocytosis

58. © 2013 Pearson Education, Inc. Endocytosis Receptor-mediated endocytosisReceptor-mediated endocytosis –Allows specific endocytosis and transcytosis Cells use to concentrate materials in limited supplyCells use to concentrate materials in limited supply –Clathrin-coated pits provide main route for endocytosis and transcytosis Uptake of enzymes, low-density lipoproteins, iron, insulin, and, unfortunately, viruses, diphtheria, and cholera toxinsUptake of enzymes, low-density lipoproteins, iron, insulin, and, unfortunately, viruses, diphtheria, and cholera toxins

59. Receptor Mediated Endocytosis No. 1 uptake methodNo. 1 uptake method in most cells in most cells Receptors and substance is internalized into a coated pit-clathrinReceptors and substance is internalized into a coated pit-clathrin Down RegulationDown Regulation

60. http://www.youtube.com/watch ?v=KiLJl3NwmpU http://www.youtube.com/watch?v=4gLtk 8Yc1Zc&feature=relatedhttp://www.youtube.com/watch?v=4gLtk 8Yc1Zc&feature=relatedhttp://www.youtube.com/watch?v=4gLtk 8Yc1Zc&feature=relatedhttp://www.youtube.com/watch?v=4gLtk 8Yc1Zc&feature=related

61. © 2013 Pearson Education, Inc. Figure 3.14b Exocytosis. Photomicrograph of a secretory vesicle releasing its contents by exocytosis (100,000x)