Human Cell Biology. General Information About the Cell. Cell Structure and Function

Transcription

1 Human Cell Biology Cell Structure and Function Learn and Understand Plasma membrane is like a picket fence Each body cell lives within a fluid environment, constantly interacting with it following the laws of chemistry and physics Protein conformation and protein ability to temporarily and reversibly change shape is key to life Cell organelles carryout specialized functions The presence and number of each organelle in a cell dictates what a cell can do General Information About the Cell Since 1830s, Basic/Smallest Unit Of Life Surface to volume ratio - Cell size is optimized What a cell can do is based on form and what it includes About 250 different cell types in adult human 1

2 General Information About the Cell Requires energy varies based on need Most contain complete set of genetic information Contain building blocks and structures to carry out activities Not created - come from the reproduction of other cells humans have trillions Basic Organization of Eukaryotic Cells - Generalized Cell All cells have some common structures and functions Human cells have three basic parts: Plasma membrane flexible outer selectivelypermeable boundary Cytoplasm intracellular fluid containing organelles Nucleus control center Smooth endoplasmic reticulum Typical Eukaryotic Animal Cell Chromatin Nucleolus Nuclear envelope Nucleus Plasma membrane Cytosol Mitochondrion Lysosome Centrioles Centrosome matrix Rough endoplasmic reticulum Ribosomes Golgi apparatus Cytoskeletal elements Microtubule Intermediate filaments Peroxisome Secretion being released from cell by exocytosis 2

3 The Cell s Environments Extracellular fluid (ECF) = interstitial fluid + blood plasma Intracellular fluid (ICF) = fluid inside cells Fluids are solutions of numerous dissolved substances (solutes) and/or colloids (suspensions, not quite soluble but dispersed like a solution) Extracellular Fluids % of Body Weight Interstitial fluid 15 Blood plasma 5 Intracellular fluid 40 Plasma Membrane The outermost membrane there are many internal membranes Separates intracellular fluid from extracellular fluid a 7-10 nm boundary Lipid bilayer and proteins in constantly changing fluid mosaic (model) Plays dynamic role in cellular activity Selectively or differentially permeable Figure 3.3 The plasma membrane. Extracellular fluid (watery environment outside cell) Note: Glycocalyx is unique to an individual s cells and identifies cells to each other. Also identifies non-self. Glycocalyx (carbohydrates) Lipid bilayer containing proteins Outward-facing layer of phospholipids Inward-facing layer of phospholipids Cytoplasm (watery environment inside cell) Polar head of phospholipid molecule Nonpolar tail of phospholipid molecule Cholesterol Glycolipid Integral proteins Filament of cytoskeleton Peripheral proteins Glycoprotein 3

4 Membrane Lipids 75% phospholipids (lipid bilayer) Phosphate heads: polar and hydrophilic Fatty acid tails: nonpolar and hydrophobic 5% glycolipids Lipids with polar sugar groups on outer membrane surface 20% cholesterol Increasing cholesterol increases membrane stability, reduces fluidity Membrane Lipids Fluid nature provides/allows Distribution of molecules within the membrane to change Growth and repair Phospholipids reassembled if membrane is damaged or altered self orienting PM incorporates other membranes or segments can break away One reason for selective permeability Phospholipids Polar (hydrophilic) at one end; nonpolar (hydrophobic) at the other. Do you remember polarity? What about electronegativity? 4

5 Membrane Proteins Improve communication with environment ½ mass of plasma membrane Most carry out specialized membrane functions Some chemically anchored and move freely Some tethered to intracellular structures Two types Membrane Proteins Integral proteins Firmly inserted into membrane most are transmembranal hydrophobic and hydrophilic regions place them in membrane Can interact with lipid tails and water Function as transport proteins (channels and carriers), enzymes, or receptors Membrane Proteins Peripheral proteins Loosely attached to integral proteins Include filaments on intracellular surface for membrane support Function as enzymes; motor proteins for shape change during cell division and muscle contraction; cell-to-cell connections 5

6 Summary of Membrane Protein Function Transport Receptors Attachment to extracellular proteins or other cells Enzymes Cell-cell recognition Critical Learning Objective: Function dependent on 3-D shape (conformation) and chemical characteristics. Conformation dependent on amino acids present, bonding, and environment Conformational Shift - a result of the R groups of the amino acids that make up the proteins Protein Basics amine Carboxyl (acid) hydrophilic Neutral/hydrophobic A dipeptide Acidic side group - hydrophilic Linear sequence of amino acids α helix β pleated sheet weakly maintained via hydrogen bonding Many fibrous proteins Globular proteins formed by hydrogen and stronger covalent bonds Hydrophilic AAs orient externally Final shape means everything the foundation of protein function 6

7 Transport Channel: A protein that spans the memb may provide a hydrophilic channel acros the membrane that is selective for a particular solute. Carrier: Some transport proteins hydroly ATP as an energy source to actively pum substances across the membrane. Not all carriers utilize ATP ATP ADP + P + free energy Signal Receptors Active site or binding site A membrane protein exposed to the outside of the cell may have a binding site that fits the shape of a specific chemical messenger, such as a hormone. When bound, the chemical messenger may cause a change in shape in the protein that initiates a chain of chemical reactions in the cell. Receptor Contact signaling touching and recognition of cells Chemical signaling interaction between receptors and ligands to alter activity of cell proteins Signal Transduction using the G protein messaging system Ligand (1st messenger) Receptor G protein Enzyme 2nd messenger Extracellular fluid Effector protein (e.g., an enzyme) Ligand Receptor G protein GDP Inactive 2nd messenger Active 2nd messenger * Ligands include hormones and neurotransmitters. Activated kinase enzymes Cascade of cellular responses (The amplification effect is tremendous. Each enzyme catalyzes hundreds of reactions.) Intracellular fluid 7

8 Enzymes Enzymatic activity membrane protein may be an enzyme with its active site exposed to substances in the adjacent solution Example: final digestion of biomolecules at membrane of intestinal cells A team of several enzymes in a membrane may catalyze sequential steps of a metabolic pathway Attachment to the internal cytoskeleton and/or extracellular matrix Elements of the cytoskeleton (cell's internal supports) and the extracellular matrix (basement membrane) may anchor to membrane proteins, which helps maintain cell shape and fix the location of certain membrane proteins. Others play a role in cell movement or bind adjacent cells together. Intercellular Joining - Cell Junctions Some cells free roaming e.g., sperm cells, several cells of immune system CAMs Many cells bound into communities Membrane proteins of adjacent cells may be hooked together in various kinds of intercellular junctions. Three ways cells are bound cell adhesion molecules or CAMs 8

9 Plasma membranes of adjacent cells Microvilli Intercellular space Basement membrane Interlocking junctional proteins Intercellular space Tight junctions: Impermeable junctions prevent molecules from passing through the intercellular space. Plasma membranes of adjacent cells Microvilli Intercellular space Basement membrane Intermediate filament (keratin) Intercellular space Plaque Linker proteins (cadherins) Desmosomes: Anchoring junctions bind adjacent cells together like a molecular Velcro and help form an internal tension-reducing network of fibers. Sheet-like tissues Plasma membranes of adjacent cells Microvilli Intercellular space Basement membrane Gap junctions: Communicating junctions allow ions and small molecules to pass for intercellular communication. Cardiac muscle, smooth muscle, some neurons Intercellular space Channel between cells (formed by connexons) 9

10 Cell-Cell Recognition Some glycoproteins serve as identification tags that are specifically recognized by other cells. Glycoprotein Passage of Materials Across the Membrane Plasma membranes selectively permeable Some molecules pass through easily; some do not Passage of a molecule is the result of chemical properties (polarity/charge), size, availability of specific channels or carriers, electrochemical gradient some substances pass easily through lipid bilayer some pass through channel and carrier proteins some must be pumped across using carrier proteins and energy some must be engulfed Types of Membrane Transport Passive processes No cellular energy (ATP) required Substance moves down its concentration or electrical gradient High to low concentration; positive charge toward negative charge; until equilibrium Diffusion Simple diffusion Osmosis, the diffusion of solvent (water) based on solute concentration If you need to, review osmosis and tonicity p Osmolarity = sum of the molarities of the dissolved particles of a solution mosm/l Facilitated diffusion assisted Carrier- and channel-mediated involves some of the those proteins just presented Influenced by temperature Filtration Based on size of openings, size of molecules, pressure More commonly occurs in-between cells rather than across membranes Active processes Energy (ATP) required which can only be provided by a living cell 10

11 Passive Processes: Figure 3.7a Diffusion through the plasma membrane. Extracellular fluid Lipidsoluble solutes Cytoplasm Simple diffusion of fat-soluble molecules directly through the phospholipid bilayer Passive Processes: Figure 3.7c Diffusion through the plasma membrane. Small lipidinsoluble solutes A leakage channel always open Compare to a gated channel that requires a stimulus to open Channel-mediated facilitated diffusion through a channel protein; mostly ions selected on basis of size and charge Passive Processes: Figure 3.7d Diffusion through the plasma membrane. Water molecules Lipid bilayer Aquaporin Osmosis, diffusion of a solvent such as water through a specific channel protein (aquaporin) or through the lipid bilayer 11

12 Passive Processes: Figure 3.7b Diffusion through the plasma membrane. Lipid-insoluble solutes (such as sugars or amino acids) Conformational shift of the protein moves the molecule Carrier-mediated facilitated Diffusion via protein carrier specific for one chemical; binding of substrate causes transport protein to change shape Carrier Protein Dynamics Lessons: Carriers/facilitators are specific, carry only compatible molecules Competitors/inhibitors alter ability to carry compatible molecules Carrying/facilitating takes time, albeit brief The number of carriers/facilitators in cell membrane is finite the cell controls the number and type up/down regulation possible Membrane Transport: Active Processes Two types of active processes Active transport Vesicular transport Both require ATP to move solutes across a living plasma membrane because: Solute too large (example: proteins) for channels and/or Solute not lipid soluble and/or No concentration gradient 12

13 Active Transport: Two Types Requires carrier proteins (solute pumps ) Bind specifically and reversibly with substance Moves solutes against concentration gradient Primary active transport Required energy directly from ATP hydrolysis Secondary active transport Required energy indirectly from ionic gradients created by primary active transport Primary Active Transport Energy from hydrolysis of ATP causes shape change in transport protein that "pumps" solutes (ions) across membrane Solute binding and phoshorylation cause conformational changes in transport protein E.g., calcium, hydrogen, Na + -K + pumps Sodium-potassium pump Most well-studied Carrier (pump) called Na + -K + ATPase Located in all plasma membranes Involved in primary and secondary active transport of nutrients and ions 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. Extracellular fluid Na + Na + K + pump ATP-binding site Cytoplasm K + Na + bound 1 Three cytoplasmic Na + bind to pump protein. P 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. Na + released K + bound P P i K + 5 K + binding triggers release of the phosphate. The dephosphorylated pump resumes its original conformation. 3 Phosphorylation causes the pump to change shape, expelling Na + to the outside. P 4 Two extracellular K + bind to pump. 13

14 Figure 3.11 Secondary active transport is driven by the concentration gradient created by primary active transport. Extracellular fluid Na+-K+ pump Na + -glucose symport transporter loads glucose from extracellular fluid Glucose Na + -glucose symport transporter releases glucose into the cytoplasm Cytoplasm Active Transport Terms: Uniport - always transports one substance at a time (not shown) Cotransport - always transports more than one substance at a time Symport system: Substances transported in same direction Antiport system: Substances transported in opposite directions Vesicular Transport Transport of large particles, macromolecules, and fluids across membrane in membranous sacs called vesicles Requires cellular energy Functions: Exocytosis transport out of cell Endocytosis transport into cell Phagocytosis, pinocytosis, receptor-mediated endocytosis Transcytosis transport into, across, and then out of cell Vesicular trafficking transport from one area or organelle in cell to another Phagocytosis and Receptor-Mediated Endocytosis pseudopods Receptors Vesicle Phagosome 14

15 Pinocytosis and Exocytosis Captured in Living Cell Vesicle Photomicrograph of a secretory vesicle releasing its contents by exocytosis (100,000x) Figure 3.12 Events of endocytosis mediated by protein-coated pits. 1 Extracellular fluid Plasma Protein coat membrane (typically clathrin) Cytoplasm 2 3 Transport vesicle Uncoated endocytic vesicle 4 Uncoated vesicle fuses with a sorting vesicle called an endosome. Lysosome Endosome 5 Transport vesicle containing membrane compone -nts moves to the plasma membrane for recycling. 6 Fused vesicle may (a) fuse with lysosome for digestion of its contents, or (b) deliver its contents to the plasma membrane on the opposite side of the cell (transcytosis). Cell Organelles 15

16 Cytoplasm Cellular material outside nucleus but inside plasma membrane Composed of Cytoskeleton Cytosol: semi-fluid portion. Dissolved molecules (ions in water) A colloid (suspension of semi-soluble substances, example: proteins in water) Cytoplasmic Inclusions granules, droplets, pigment molecules, crystals Organelles Nucleus Membrane-bound Nucleoplasm, nucleolus and nuclear envelope Much of the DNA in a cell located here Figure 3.29a The nucleus. Nuclear envelope Chromatin (condensed) Nucleolus Nuclear pores Nucleus Cisterns of rough ER 16

17 Cytoskeleton Supports the cell but has to allow for movements like changes in cell shape and movements of cilia Microtubules: hollow, made of tubulin. Internal scaffold, transport, cell division Intermediate filaments: mechanical strength Microfilaments: actin. Structure, support for microvilli, contractility, movement Cytoplasmic inclusions: aggregates of chemicals such as lipid droplets, melanin Cytoplasmic Organelles Membranous Mitochondria Peroxisomes Lysosomes Endoplasmic reticulum Golgi apparatus Nonmembranous Cytoskeleton Centrioles Ribosomes Membranes allow crucial compartmentalization Ribosomes Sites of protein synthesis Composed of a large and a small rrna subunit Types Free Attached (to endoplasmic reticulum) 17

18 Endoplasmic Reticulum Types Rough Has attached ribosomes Proteins produced and modified here Common in cells that secrete protein products Smooth No attached ribosomes, instead integral proteins serving as enzymes Manufacturing, metabolism, breakdown More specialized function in muscle cells Cisternae: Interior spaces isolated from rest of cytoplasm Figure 3.18 The endoplasmic reticulum. Nucleus Smooth ER Nuclear envelope Rough ER Ribosomes Diagrammatic view of smooth and rough ER Electron micrograph of smooth and rough ER (25,000x) Figure 3.39 Rough ER processing of proteins. Slide 1 1 The SRP directs the 2 Once attached to the ER, the SRP is mrna-ribosome complex to the released and the growing polypeptide rough ER. There the SRP binds to snakes through the ER membrane pore a receptor site. into the cistern. ER signal sequence Ribosome mrna 3 An enzyme clips off the signal sequence. As protein synthesis continues, sugar groups may be added to the protein. Signal recognition particle (SRP) Receptor site Signal sequence removed Growing polypeptide Released protein Sugar group 4 In this example, the completed protein is released from the ribosome and folds into its 3-D conformation, a process aided by molecular chaperones. 5 The protein is enclosed within a protein coated transport vesicle. The transport vesicles make their way to the Golgi apparatus, where further processing of the proteins occurs (see Figure 3.19). Rough ER cistern Cytosol Transport vesicle pinching off Protein-coated transport vesicle 18

19 Figure 3.19a Golgi apparatus. Transport vesicle from rough ER Cis face receiving side of Golgi apparatus Cisterns New vesicles forming Transport vesicle from trans face Secretory vesicle Trans face shipping side of Golgi apparatus Many vesicles in the process of pinching off from the Golgi apparatus. Figure 3.20 The sequence of events from protein synthesis on the rough ER to the final distribution of those proteins. Rough ER ER membrane Phagosome Proteins in cisterns Plasma membrane Vesicular trafficking Pathway C: Lysosome containing acid hydrolase Vesicle enzymes becomes lysosome Golgi apparatus Pathway A: Vesicle contents destined for exocytosis Secretory vesicle Secretion by exocytosis Pathway B: Vesicle membrane to be incorporated into plasma membrane Extracellular fluid Action of Lysosomes 19

20 Mitochondria Major site of ATP synthesis Membranes Cristae: Infoldings of inner membrane Matrix: Substance located in space formed by inner membrane Mitochondria increase in number when cell energy requirements increase. Mitochondria contain DNA that codes for some of the proteins needed for mitochondria production. Overview of Cell Metabolism Production of ATP necessary for life ATP production takes place in the cytosol (anaerobic) and mitochondria (aerobic) Anaerobic does not require oxygen. Results in very little ATP production but provides ATP when O 2 is in short supply. Aerobic requires oxygen. Results in large amount of ATP. Cilia Appendages projecting from cell surfaces Capable of movement Moves materials over the cell surface 20

21 Flagella Similar to cilia but longer Usually only one per cell Move the cell itself in wave-like fashion Example: sperm cell 21