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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 Department of Kinesiology and Applied Physiology WCR 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. Department of Kinesiology and Applied Physiology 2 Erythrocytes Fibroblasts Epithelial cells (a) Cells that connect body parts, form linings, or transport gases Skeletal Muscle cell Smooth muscle cells (b) Cells that move organs and body parts Macrophage Nerve cell (e) Cell that gathers information and control body functions (f) Cell of reproduction Sperm Fat cell (c) Cell that stores (d) Cell that nutrients fights disease Figure 3.1 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 Chromatin Nucleolus Nuclear envelope Nucleus Smooth endoplasmic reticulum Mitochondrion Cytosol Lysosome Centrioles Centrosome matrix Cytoskeletal elements • Microtubule • Intermediate filaments Copyright © 2010 Pearson Education, Inc. Plasma membrane Rough endoplasmic reticulum Ribosomes Golgi apparatus Secretion being released from cell by exocytosis Peroxisome Figure 3.2 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 Extracellular fluid (watery environment) Polar head of phospholipid molecule Cholesterol Glycolipid Glycoprotein Carbohydrate of glycocalyx Outwardfacing layer of phospholipids Integral proteins Filament of cytoskeleton Peripheral Bimolecular Inward-facing proteins lipid layer layer of containing phospholipids Nonpolar proteins tail of phospholipid Cytoplasm molecule (watery environment) Copyright © 2010 Pearson Education, Inc. Figure 3.3 Membrane Proteins • Integral proteins – Firmly inserted into the membrane (most are transmembrane) – Functions: • Transport proteins (channels and carriers), enzymes, or receptors PLAY Animation: Transport Proteins 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 PLAY Animation: Structural Proteins PLAY Animation: Receptor Proteins (a) Transport 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. Copyright © 2010 Pearson Education, Inc. Figure 3.4a Signal Receptor Copyright © 2010 Pearson Education, Inc. (b) Receptors for signal transduction 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. Figure 3.4b (c) Attachment to the cytoskeleton and extracellular matrix (ECM) 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. Copyright © 2010 Pearson Education, Inc. Figure 3.4c (d) Enzymatic activity Enzymes Copyright © 2010 Pearson Education, Inc. 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. Figure 3.4d (e) Intercellular joining 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 Copyright © 2010 Pearson Education, Inc. Figure 3.4e (f) Cell-cell recognition Some glycoproteins (proteins bonded to short chains of sugars) serve as identification tags that are specifically recognized by other cells. Glycoprotein Copyright © 2010 Pearson Education, Inc. Figure 3.4f Membrane Junctions • Three types: – Tight junction – Desmosome – Gap junction Plasma membranes of adjacent cells Microvilli Intercellular space Basement membrane Interlocking junctional proteins Intercellular space (a) Tight junctions: Impermeable junctions prevent molecules from passing through the intercellular space. Copyright © 2010 Pearson Education, Inc. Figure 3.5a Plasma membranes of adjacent cells Microvilli Intercellular space Basement membrane Intercellular space Plaque Intermediate filament (keratin) Linker glycoproteins (cadherins) (b) Desmosomes: Anchoring junctions bind adjacent cells together and help form an internal tension-reducing network of fibers. Copyright © 2010 Pearson Education, Inc. Figure 3.5b Plasma membranes of adjacent cells Microvilli Intercellular space Basement membrane Intercellular space Channel between cells (connexon) (c) Gap junctions: Communicating junctions allow ions and small molecules to pass from one cell to the next for intercellular communication. Copyright © 2010 Pearson Education, Inc. Figure 3.5c 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 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 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 Copyright © 2010 Pearson Education, Inc. Passive Processes • Simple diffusion • Carrier-mediated facilitated diffusion • Channel-mediated facilitated diffusion • Osmosis Copyright © 2010 Pearson Education, Inc. Passive Processes: Simple Diffusion • Nonpolar lipid-soluble (hydrophobic) substances diffuse directly through the phospholipid bilayer PLAY Animation: Diffusion Copyright © 2010 Pearson Education, Inc. Extracellular fluid Lipidsoluble solutes Cytoplasm (a) Simple diffusion of fat-soluble molecules directly through the phospholipid bilayer Copyright © 2010 Pearson Education, Inc. Figure 3.7a 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 Copyright © 2010 Pearson Education, Inc. 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 Copyright © 2010 Pearson Education, Inc. Figure 3.7b Small lipidinsoluble solutes (c) Channel-mediated facilitated diffusion through a channel protein; mostly ions selected on basis of size and charge Copyright © 2010 Pearson Education, Inc. Figure 3.7c 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 Copyright © 2010 Pearson Education, Inc. 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 Copyright © 2010 Pearson Education, Inc. Figure 3.7d Importance of Osmosis • When osmosis occurs, water enters or leaves a cell • Change in cell volume disrupts cell function PLAY Animation: Osmosis 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 Copyright © 2010 Pearson Education, Inc. Summary of Passive Processes Process Simple diffusion Facilitated diffusion Osmosis Energy Source Kinetic energy Kinetic energy Kinetic energy • Also see Table 3.1 Copyright © 2010 Pearson Education, Inc. Example Movement of O2 through phospholipid bilayer Movement of glucose into cells Movement of H2O through phospholipid bilayer or AQPs Membrane Transport: Active Processes • Two types of active processes: • Active transport • Vesicular transport • Both use ATP to move solutes across a living plasma membrane 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 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 Copyright © 2010 Pearson Education, Inc. Extracellular fluid Na+ Na+-K+ pump Na+ bound K+ ATP-binding site Cytoplasm 1 Cytoplasmic Na+ binds to pump protein. P ATP K+ released ADP 6 K+ is released from the pump protein and Na+ sites are ready to bind Na+ again. The cycle repeats. 2 Binding of Na+ promotes phosphorylation of the protein by ATP. Na+ released K+ bound P Pi K+ 5 K+ binding triggers release of the phosphate. Pump protein returns to its original conformation. 3 Phosphorylation causes the protein to change shape, expelling Na+ to the outside. P 4 Extracellular K+ binds to pump protein. Copyright © 2010 Pearson Education, Inc. Figure 3.10 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 Copyright © 2010 Pearson Education, Inc. Extracellular fluid Glucose Na+-K+ pump Na+-glucose symport transporter loading glucose from ECF Na+-glucose symport transporter releasing glucose into the cytoplasm Cytoplasm 1 The ATP-driven Na+-K+ pump 2 As Na+ diffuses back across the stores energy by creating a steep concentration gradient for Na+ entry into the cell. membrane through a membrane cotransporter protein, it drives glucose against its concentration gradient into the cell. (ECF = extracellular fluid) Copyright © 2010 Pearson Education, Inc. Figure 3.11 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 Copyright © 2010 Pearson Education, Inc. Phagosome Copyright © 2010 Pearson Education, Inc. (a) Endocytosis: Phagocytosis The cell engulfs a large particle by forming projecting pseudopods (“false feet”) around it and enclosing 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 proteincoated but has receptors capable of binding to microorganisms or solid particles. Figure 3.13a (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. Vesicle Copyright © 2010 Pearson Education, Inc. Figure 3.13b Vesicle Receptor recycled to plasma membrane Copyright © 2010 Pearson Education, Inc. (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. Figure 3.13c Exocytosis Plasma membrane Extracellular SNARE (t-SNARE) fluid Secretory vesicle Vesicle SNARE (v-SNARE) Molecule to be secreted Cytoplasm Fusion pore formed 1 Membrane- bound vesicle migrates to plasma membrane. 2 Proteins at vesicle surface (vFused SNAREs) bind with v- and t-SNAREs (plasma t-SNAREs membrane proteins). Copyright © 2010 Pearson Education, Inc. 3 Vesicle and plasma membrane fuse and pore opens up. 4 Vesicle contents released to cell exterior. Figure 3.14a Summary of Active Processes Process Energy Source Example Primary active transport ATP Pumping of ions across membranes Secondary active transport Ion gradient Movement of polar or charged solutes across membranes Exocytosis ATP Secretion of hormones and neurotransmitters Phagocytosis ATP White blood cell phagocytosis Pinocytosis ATP Absorption by intestinal cells Receptor-mediated endocytosis ATP Hormone and cholesterol uptake Copyright © 2010 Pearson Education, Inc.