1. Department of Kinesiology and Applied Physiology WCR Chapter 3: Cells Overview Plasma membrane: structure Plasma membrane: transport Resting membrane potential Cell-environment interactions Cytoplasm Nucleus Cell growth & reproduction Extracellular materials Developmental aspects

2. Department of Kinesiology and Applied Physiology2 Do exercise scientists need to think about cells? Exercise in a Pill “AMPK and PPARδ Agonists Are Exercise Mimetics” AICAR activates intracellular pathways that are also activated by exercise. Mice taking AICAR look like mice on exercise. Mice on AICAR plus exercise are supermice. Narkar et al., Cell 2008.

3. Fibroblasts Erythrocytes Epithelial cells (d) Cell that fights disease Nerve cell Fat cell Sperm (a) Cells that connect body parts, form linings, or transport gases (c) Cell that stores nutrients (b) Cells that move organs and body parts (e) Cell that gathers information and control body functions (f) Cell of reproduction Skeletal Muscle cell Smooth muscle cells Macrophage Figure 3.1

4. Generalized Cell All cells have some common structures and functions Human cells have three basic parts: – Plasma membrane—flexible outer boundary – Cytoplasm—intracellular fluid containing organelles – Nucleus—control center

5. Copyright © 2010 Pearson Education, Inc. Figure 3.2 Secretion being released from cell by exocytosis Peroxisome Ribosomes Rough endoplasmic reticulum Nucleus Nuclear envelope Chromatin Golgi apparatus Nucleolus Smooth endoplasmic reticulum Cytosol Lysosome Mitochondrion Centrioles Centrosome matrix Cytoskeletal elements Microtubule Intermediate filaments Plasma membrane

6. Plasma Membrane Bimolecular layer of lipids and proteins in a constantly changing fluid mosaic Plays a dynamic role in cellular activity Separates intracellular fluid from extracellular fluid – Interstitial fluid = ECF that surrounds cells

7. Copyright © 2010 Pearson Education, Inc. Figure 3.3 Integral proteins Extracellular fluid (watery environment) Cytoplasm (watery environment) Polar head of phospholipid molecule Glycolipid Cholesterol Peripheral proteins Bimolecular lipid layer containing proteins Inward-facing layer of phospholipids Outward- facing layer of phospholipids Carbohydrate of glycocalyx Glycoprotein Filament of cytoskeleton Nonpolar tail of phospholipid molecule

8. Membrane Proteins Integral proteins – Firmly inserted into the membrane (most are transmembrane) – Functions: Transport proteins (channels and carriers), enzymes, or receptors Animation: Transport Proteins PLAY

9. Membrane Proteins Peripheral proteins – Loosely attached to integral proteins – Include filaments on intracellular surface and glycoproteins on extracellular surface – Functions: Enzymes, motor proteins, cell-to-cell links, provide support on intracellular surface, and form part of glycocalyx Animation: Structural Proteins PLAY Animation: Receptor Proteins PLAY

10. Copyright © 2010 Pearson Education, Inc. Figure 3.4a A protein (left) that spans the membrane may provide a hydrophilic channel across the membrane that is selective for a particular solute. Some transport proteins (right) hydrolyze ATP as an energy source to actively pump substances across the membrane. (a) Transport

11. Copyright © 2010 Pearson Education, Inc. Figure 3.4b A membrane protein exposed to the outside of the cell may have a binding site with a specific shape that fits the shape of a chemical messenger, such as a hormone. The external signal may cause a change in shape in the protein that initiates a chain of chemical reactions in the cell. (b) Receptors for signal transduction Signal Receptor

12. Copyright © 2010 Pearson Education, Inc. Figure 3.4c Elements of the cytoskeleton (cell’s internal supports) and the extracellular matrix (fibers and other substances outside the cell) may be anchored to membrane proteins, which help maintain cell shape and fix the location of certain membrane proteins. Others play a role in cell movement or bind adjacent cells together. (c) Attachment to the cytoskeleton and extracellular matrix (ECM)

13. Copyright © 2010 Pearson Education, Inc. Figure 3.4d A protein built into the membrane may be an enzyme with its active site exposed to substances in the adjacent solution. In some cases, several enzymes in a membrane act as a team that catalyzes sequential steps of a metabolic pathway as indicated (left to right) here. (d) Enzymatic activity Enzymes

14. Copyright © 2010 Pearson Education, Inc. Figure 3.4e Membrane proteins of adjacent cells may be hooked together in various kinds of intercellular junctions. Some membrane proteins (CAMs) of this group provide temporary binding sites that guide cell migration and other cell-to-cell interactions. CAMs (e) Intercellular joining

15. Copyright © 2010 Pearson Education, Inc. Figure 3.4f Some glycoproteins (proteins bonded to short chains of sugars) serve as identification tags that are specifically recognized by other cells. (f) Cell-cell recognition Glycoprotein

16. Membrane Junctions Three types: – Tight junction – Desmosome – Gap junction

17. Copyright © 2010 Pearson Education, Inc. Figure 3.5a Interlocking junctional proteins Intercellular space Plasma membranes of adjacent cells Microvilli Intercellular space Basement membrane (a) Tight junctions: Impermeable junctions prevent molecules from passing through the intercellular space.

18. Copyright © 2010 Pearson Education, Inc. Figure 3.5b Intercellular space Plasma membranes of adjacent cells Microvilli Intercellular space Plaque Linker glycoproteins (cadherins) Intermediate filament (keratin) (b) Desmosomes: Anchoring junctions bind adjacent cells together and help form an internal tension-reducing network of fibers. Basement membrane

19. Copyright © 2010 Pearson Education, Inc. Figure 3.5c Plasma membranes of adjacent cells Microvilli Intercellular space Intercellular space Channel between cells (connexon) (c) Gap junctions: Communicating junctions allow ions and small mole- cules to pass from one cell to the next for intercellular communication. Basement membrane

20. Membrane Transport: How things get in and out of cells Plasma membranes are selectively permeable: some molecules easily pass through the membrane; others do not

21. Types of Membrane Transport Passive processes – No cellular energy (ATP) required – Substance moves down its concentration gradient Active processes – Energy (ATP) required – Occurs only in living cell membranes

22. Copyright © 2010 Pearson Education, Inc. Passive Processes What determines whether or not a substance can passively permeate a membrane? 1.Lipid solubility of substance 2.Channels of appropriate size 3.Carrier proteins PLAY Animation: Membrane Permeability

23. Copyright © 2010 Pearson Education, Inc. Passive Processes Simple diffusion Carrier-mediated facilitated diffusion Channel-mediated facilitated diffusion Osmosis

24. Copyright © 2010 Pearson Education, Inc. Passive Processes: Simple Diffusion Nonpolar lipid-soluble (hydrophobic) substances diffuse directly through the phospholipid bilayer PLAY Animation: Diffusion

25. Copyright © 2010 Pearson Education, Inc. Figure 3.7a Extracellular fluid Lipid- soluble solutes Cytoplasm (a) Simple diffusion of fat-soluble molecules directly through the phospholipid bilayer

26. Copyright © 2010 Pearson Education, Inc. Passive Processes: Facilitated Diffusion Certain lipophobic molecules (e.g., glucose, amino acids, and ions) use carrier proteins or channel proteins, both of which: Exhibit specificity (selectivity) Are saturable; rate is determined by number of carriers or channels Can be regulated in terms of activity and quantity

27. Copyright © 2010 Pearson Education, Inc. Figure 3.7b Lipid-insoluble solutes (such as sugars or amino acids) (b) Carrier-mediated facilitated diffusion via a protein carrier specific for one chemical; binding of substrate causes shape change in transport protein

28. Copyright © 2010 Pearson Education, Inc. Figure 3.7c Small lipid- insoluble solutes (c) Channel-mediated facilitated diffusion through a channel protein; mostly ions selected on basis of size and charge

29. Copyright © 2010 Pearson Education, Inc. Passive Processes: Osmosis Movement of solvent (water) across a selectively permeable membrane Water diffuses through plasma membranes: Through the lipid bilayer Through water channels called aquaporins

30. Copyright © 2010 Pearson Education, Inc. Figure 3.7d Water molecules Lipid billayer Aquaporin (d) Osmosis, diffusion of a solvent such as water through a specific channel protein (aquaporin) or through the lipid bilayer

31. Copyright © 2010 Pearson Education, Inc. Importance of Osmosis When osmosis occurs, water enters or leaves a cell Change in cell volume disrupts cell function PLAY Animation: Osmosis

32. Copyright © 2010 Pearson Education, Inc. Tonicity Tonicity: How much dissolved material there is in a solution. Tonicity determines whether a solution will make cells shrink or swell. Isotonic: A solution with the same solute concentration as the inside of a normal cell Hypertonic: A solution with a greater solute concentration than than a normal cell Hypotonic: A solution with a lesser solute concentration than a normal cell

33. Copyright © 2010 Pearson Education, Inc. Summary of Passive Processes Also see Table 3.1 ProcessEnergy Source Example Simple diffusion Kinetic energy Movement of O 2 through phospholipid bilayer Facilitated diffusion Kinetic energy Movement of glucose into cells OsmosisKinetic energy Movement of H 2 O through phospholipid bilayer or AQPs

34. Copyright © 2010 Pearson Education, Inc. Membrane Transport: Active Processes Two types of active processes: Active transport Vesicular transport Both use ATP to move solutes across a living plasma membrane

35. Copyright © 2010 Pearson Education, Inc. Active Transport Requires carrier proteins (solute pumps) Moves solutes against a concentration gradient Types of active transport: Primary active transport Secondary active transport

36. Copyright © 2010 Pearson Education, Inc. Primary Active Transport Energy from breakdown of ATP causes shape change in transport protein to “pump” molecules across the membrane Example: Sodium-potassium pump (Na + -K + ATPase) Located in all plasma membranes Involved in primary and secondary active transport of nutrients and ions Maintains “electrochemical gradients” essential for functions of muscle and nerve tissues

37. Copyright © 2010 Pearson Education, Inc. Figure 3.10 Extracellular fluid K + is released from the pump protein and Na + sites are ready to bind Na + again. The cycle repeats. Binding of Na+ promotes phosphorylation of the protein by ATP. Cytoplasmic Na + binds to pump protein. Na + Na + -K + pump K + released ATP-binding site Na + bound Cytoplasm ATP ADP P K+K+ K + binding triggers release of the phosphate. Pump protein returns to its original conformation. Phosphorylation causes the protein to change shape, expelling Na + to the outside. Extracellular K + binds to pump protein. Na + released K + bound P K+K+ P PiPi 1 2 3 4 5 6

38. Copyright © 2010 Pearson Education, Inc. Secondary Active Transport Energy stored in ionic gradients is used indirectly to drive transport of other solutes Always involves cotransport – transport of more than one substance at a time Two substances transported in same direction (Na+, glucose) Two substances transported in opposite directions (Na+, H+) Mod WCR

39. Copyright © 2010 Pearson Education, Inc. Figure 3.11 The ATP-driven Na + -K + pump stores energy by creating a steep concentration gradient for Na + entry into the cell. As Na + diffuses back across the membrane through a membrane cotransporter protein, it drives glucose against its concentration gradient into the cell. (ECF = extracellular fluid) Na + -glucose symport transporter loading glucose from ECF Na + -glucose symport transporter releasing glucose into the cytoplasm Glucose Na + -K + pump Cytoplasm Extracellular fluid 12

40. Copyright © 2010 Pearson Education, Inc. Vesicular Transport Transport of large particles, macromolecules, and fluids across plasma membranes Requires cellular energy (e.g., ATP) Functions: Exocytosis—transport out of cell Endocytosis—transport into cell (receptor mediated; phago-; pino-) Transcytosis—transport into, across, and then out of cell Vesicular transport within a cell (see the video) Mod WCR

41. Copyright © 2010 Pearson Education, Inc. Figure 3.13a Phagosome (a)Endocytosis: Phagocytosis The cell engulfs a large particle by forming pro- jecting pseudopods (“false feet”) around it and en- closing it within a membrane sac called a phagosome. The phagosome is combined with a lysosome. Undigested contents remain in the vesicle (now called a residual body) or are ejected by exocytosis. Vesicle may or may not be protein- coated but has receptors capable of binding to microorganisms or solid particles.

42. Copyright © 2010 Pearson Education, Inc. Figure 3.13b Vesicle (b) Endocytosis: Pinocytosis The cell “gulps” drops of extracellular fluid containing solutes into tiny vesicles. No receptors are used, so the process is nonspecific. Most vesicles are protein-coated.

43. Copyright © 2010 Pearson Education, Inc. Figure 3.13c Vesicle Receptor recycled to plasma membrane (c) Receptor-mediated endocytosis Extracellular substances bind to specific receptor proteins in regions of coated pits, enabling the cell to ingest and concentrate specific substances (ligands) in protein-coated vesicles. Ligands may simply be released inside the cell, or combined with a lysosome to digest contents. Receptors are recycled to the plasma membrane in vesicles.

44. Copyright © 2010 Pearson Education, Inc. Figure 3.14a 1 Membrane- bound vesicle migrates to plasma membrane. 2 Proteins at vesicle surface (v- SNAREs) bind with t-SNAREs (plasma membrane proteins). Exocytosis Extracellular fluid Plasma membrane SNARE (t-SNARE) Secretory vesicle Vesicle SNARE (v-SNARE) Molecule to be secreted Cytoplasm Fused v- and t-SNAREs 3 Vesicle and plasma membrane fuse and pore opens up. 4 Vesicle contents released to cell exterior. Fusion pore formed

45. Copyright © 2010 Pearson Education, Inc. Summary of Active Processes ProcessEnergy SourceExample Primary active transportATPPumping of ions across membranes Secondary active transport Ion gradientMovement of polar or charged solutes across membranes ExocytosisATPSecretion of hormones and neurotransmitters PhagocytosisATPWhite blood cell phagocytosis PinocytosisATPAbsorption by intestinal cells Receptor-mediated endocytosis ATPHormone and cholesterol uptake