TRENDS IN CELL BIOLOGY ABS-931 3(3-0)

Transcription

1 TRENDS IN CELL BIOLOGY ABS-931 3(3-0)

2 Course Contents: Introduction Cell Organization Cell Architecture Membrane Structure and Function Bio Transport Vesicular Transport Transport Signals Nuclear Transport Bio Energetic Mitochondrial Energy Conversion Chloroplast Energy Conversion Cytoskeleton Cell Shape Cell Contractility Cell to cell Communication Electrochemical Signaling Synaptic and Sensory Transduction Biochemical Signaling Receptor Ligand Interactions Second Messengers Signaling Cascades Cell Cycle and Apoptosis Phases of Cell Cycle and Cell Division Regulation of Cell Growth and Death Specialized Cell Systems

3 Recommended Books: The Cell by Bruce Albert and Dennis Bray, 4 th Ed. Garland Publishing Inc, New York and London. Biochemistry by Victor L. Davidson, Donald B. Sittman. 3 rd Ed. 1993, Harwal Pub Co. Cell and Molecular Biology by Gerald Karp. 1996, John Willey and Sons, Inc. London Gene VIII By Lewin Benjamin Eds Oxford University press, Inc, New york. Molecular Biology of the Gene by Watson, J. D., T. A. Baker, S. P. Bell, A. Gann, M. Levine, and R. Losick, 5th Ed New York, Benjamin Cummings ISBN X

4 Policies First 1 hr Test 17.5 % Second 1 hr Test 17.5 % Assignments (3-6) 5-10 % Quizzes (3-6) 5-10 % Terminal Exam (3 hrs) 50 % Please turn off your cell phones during class

5 What is cell Biology?

6 What is cell Biology? Divisions in the biological sciences are based on degrees of complexity

7 Biochemistry & Biophysics: study of the structures and behaviors of molecules

8 Microbiology: study of prokaryotic cells and viruses

9 Cell Biology: study of the structure and function of eukaryotic cells Developmental Biology: study of how communities of cells form tissues, organs, and build an organism

10 Anatomy & Physiology: study of the structures and functions of tissues and organs

11 Zoology & Plant Biology: study of the organisms

12 Ecology: study of how organisms interact with each other and with their environments

13 Levels of Biological Complexity 1. Biochemistry & Biophysics 2. Microbiology 3. Cell Biology 4. Developmental Biology 5. Anatomy & Physiology 6. Zoology & Plant Biology 7. Ecology

14 Understanding cell biology is important to understand the basis for disease Hypercholesterolemia (defective uptake of lipoproteins) Cystic fibrosis (misfolding of key protein) Hypertension (defective cell-cell adhesion in the kidney) Congenital heart defects (errors in cell migration during development) Muscular dystrophy (defective attachment of the plasma membrane to the cytoskeleton) Lysosomal storage disease (defective intracellular transport of enzymes) Food-borne illness (Salmonella, E. coli) Cancer (errors in cell division, migration, cell polarity, growth, etc) Ageing All disease states are caused at the cellular level

15 Understanding cell biology is important to make informed decisions on social issues Genetic engineering of foods Biotechnology Organ growth in culture Stem cell research Forensic sciences Archaeology

16 CELL BIOLOGY The Dynamic Cell Basic unit of organization or structure of all living matter

17 A brief History Galileo Galilei (Early Seventeenth century) used lenses Beginning of the study of cells as the basis of life Robert Hooke (Middle of Seventeenth century) microscopic examination of sliced cork Used Latin word cella (small room) Anton van Leeuwenhoek (Late Seventeenth century) Improved lenses, Improved magnification Robert Brown (1831) observed nucleus as opaque spot Methias Schleiden (1838) Theodore Schwann (1839) Cell Theory

18 Cell theory, definitions "Cells are of universal occurrence and are the basic units of an organism Rudolf Virchow (1859) All cells come from pre-existing cells During 20 th century A.G. Loewy and P. Siekevitz (1963) a unit of biological activity delimited by a semipermeable membrane and capable of self-reproduction in a medium free of other living systems Wilson and Morrison (1966) an integrated and continuously changing system John Paul (1970) the simplest integrated organization in living systems, capable of independent survival.

19 Principles of Cell Theory All living things are made of cells Smallest living unit of structure and function of all organisms is the cell All cells arise from preexisting cells (this principle discarded the idea of spontaneous generation)

20 Cell Size

21 Cells Have Large Surface Area-to-Volume Ratio

22 Common functional and structural properties of cells 1. Plasma membrane The plasma membrane forms a boundary between the living cell and its surroundings. The plasma membrane regulates the passage of materials into and out of the cell. 2. Cytoplasm (solution portion CYTOSOL) Chemical reactions take place in the cytoplasm transforming the energy and material needed for cell growth and reproduction. The cytoplasm consists of a soluble, called cytosol, and various particulate structures. 3. Genetic material Each cell contains a copy of the hereditary information. 4. Ribosomes 5. Utilizes energy from ATP Each cell utilizes energy from ATP, the universal energy currency of living cells. Cells carry out metabolism through which they generate ATP and cell constituents for growth and reproduction.

23 Cell Types Prokaryotic Eukaryotic

24 Cell Organization Prokaryotic cell Eukaryotic cell

25 Prokaryotic cells First cell type on earth Single cell organisms Two main types: bacteria and archaea Relatively simple structure No membrane bound nucleus Nucleoid = region of DNA concentration Organelles not bound by membranes

26 Single cell or multicellular organisms Eukaryotic cells Plants and animals Structurally more complex: organelles, cytoskeleton Nucleus bound by membrane Include fungi, protists, plant, and animal cells Possess many organelles

27 Representative Animal Cell

28 Representative Plant Cell

29 Organelles Cellular machinery Two general kinds Derived from membranes Bacteria-like organelles

30 Bacteria-Like Organelles Derived from symbiotic bacteria Ancient association Endosymbiotic theory Evolution of modern cells from cells & symbiotic bacteria

31 Prokaryotic cells vs Eukaryotic cell 1. Eukaryotic cells have a true nucleus, bound by a double membrane. Prokaryotic cells have no nucleus. 2. Eukaryotic DNA is linear; prokaryotic DNA is circular (it has no ends). 3. Eukaryotic DNA is complexed with proteins called "histones," and is organized into chromosomes; prokaryotic DNA is "naked," meaning that it has no histones associated with it, and it is not formed into chromosomes. A eukaryotic cell contains a number of chromosomes; a prokaryotic cell contains only one circular DNA molecule and a varied assortment of much smaller circlets of DNA called "plasmids." The smaller, simpler prokaryotic cell requires far fewer genes to operate than the eukaryotic cell. 4. Both cell types have ribosomes, but the ribosomes of the eukaryotic cells are larger and more complex than those of the prokaryotic cell. 5. The cytoplasm of eukaryotic cells is filled with a large, complex collection of organelles, many of them enclosed in their own membranes; the prokaryotic cell contains no membrane-bound organelles which are independent of the plasma membrane. Many of these structures, like the nucleus, increase the efficiency of functions by confining them within smaller spaces within the huge cell, or with communication and movement within the cell.

32 Comparison of features of prokaryotic and eukaryotic cells Prokaryotes Eukaryotes Typical organisms Bacteria, Archaea Protists, Fungi, Plants and Animals Typical size ~ 1-10 µm ~ µm (Sperm cells are smaller) Type of nucleus nucleoid region real nucleus with double membrane DNA RNA-/proteinsynthesis circular (usually) coupled in cytoplasm linear molecules (chromosomes) with histone proteins RNA-synthesis inside the nucleus protein synthesis in cytoplasm Ribosomes 50S+30S 60S+40S Cytoplasmatic structure very few structures highly structured by endomembranes and a cytoskeleton Cell movement flagella made of flagellin flagella and cilia made of tubulin, lamellipodia Mitochondria None one to several thousand (though some lack mitochondria) Chloroplasts None in algae and plants Organization usually single cells single cells, colonies, higher multicellular organisms with specialized cells Cell division Binary fission Mitosis (fission or budding), Meiosis

33 Eukaryotic Cells Evolved from a Symbiosis As predators (engulfing eubacteria) by animal cells Origin of Mitochondria from aerobic bacteria From hunting to Farming (engulfing photosynthetic bacteria) by plant cells Chloroplast origin Scavengers (from hunters) feed on other cells Fungi: Do not posses chloroplast but cell wall

34 Us vs. Them - Eukaryotes and Prokaryotes

35 Internal Organization of the cell

36 Common functional and structural properties of cells 1. Plasma membrane 2. Cytoplasm (solution portion CYTOSOL) 3. Genetic material 4. Ribosomes 5. Utilizes energy from ATP

37 Major Divisions of the Eukaryotic Cell

38 The Plasma Membrane Gateway to the Cell

39 Plasma Membrane Crucial to the life of the cell, encloses the cell, defines its boundaries, and maintains the essential differences between the cytosol and the extracellular environment. Inside eukaryotic cells, the membranes of the endoplasmic reticulum, Golgi apparatus, mitochondria, and other membraneenclosed organelles maintain the characteristic differences between the contents of each organelle and the cytosol. Ion gradients across membranes, established by the activities of specialized membrane proteins, can be used to synthesize ATP, to drive the transmembrane movement of selected solutes, or, in nerve and muscle cells, to produce and transmit electrical signals.

40 In all cells, the plasma membrane also contains proteins that act as sensors of external signals, allowing the cell to change its behavior in response to environmental cues; these protein sensors, or receptors, transfer information rather than ions or molecules across the membrane. Despite their differing functions, all biological membranes have a common general structure: each is a very thin film of lipid and protein molecules, held together mainly by noncovalent interactions. Cell membranes are dynamic, fluid structures, and most of their molecules are able to move about in the plane of the membrane.

41 The lipid molecules are arranged as a continuous double layer about 5 nm thick. This lipid bilayer provides the basic fluid structure of the membrane and serves as a relatively impermeable barrier to the passage of most water-soluble molecules. Protein molecules that span the lipid bilayer mediate nearly all of the other functions of the membrane, transporting specific molecules across it, for example, or catalyzing membrane-associated reactions, such as ATP synthesis.

42 In the plasma membrane, some proteins serve as structural links that connect the cytoskeleton through the lipid bilayer to either the extracellular matrix or an adjacent cell, while others serve as receptors to detect and transduce chemical signals in the cell's environment. It takes many different membrane proteins to enable a cell to function and interact with its environment. In fact, it is estimated that about 30% of the proteins that are encoded in an animal cell's genome are membrane proteins.

43 Membrane functions 1. Compartmentalization 1. Allows specialized activities to proceed without external interference 2. Enables cellular activities to be regulated independently 3. Prevents mixing of various contents 2. Providing a selectively permeable membrane 1. Prevents free interchange o material to-and-fro 2. Provides means of communication between spaces 3. PM ensures the entry of appropriate substance into cytoplasm and inappropriate substance are kept out (selectively permeable) 3. Transporting solutes 1. Physical transport of substances into and out of cell 2. Accumulation of sugars and amino acids necessary to fuel its metabolism and build its macromolecules

44 4. Responding to external signals 1. Transfer of information from one side to other through ligand receptor interaction (signal transduction) 5. Intracellular interactions 1. PM mediates interaction between the cells 2. Recognition, adherence and exchange of material and information between cells 6. Scaffolding of biochemical activities 1. Provide framework for effective interaction of components 2. Localization of enzymatic machinery 7. Energy transduction 1. Energy conversion of 1. Sunlight to chemical energy contained in carbohydrates (photosynthesis) 2. Transfer of chemical energy from carbohydrates and fats into ATP (in mitochondria and chloroplast) 2. Sites of energy storage to run cellular activities

45 The Plasma Membrane is Semipermeable The physical properties of phospholipids account for membrane assembly and many of its properties. Small molecules and larger hydrophobic molecules move through. Ions, hydrophilic molecules larger than water, and large molecules such as proteins do not move through the membrane on their own.

46 History of structure of cell membrane a) Davidson-Danielli model (1954) b) The Fluid Mosaic model (Singer & Nicolson, 1972) c) Current representation of Plasma Membrane

47 Membrane Components

48 Plasma membrane Cytosolic face (internal face) Exoplasmic face (external face) What about organelles? Lysosome - Mitochondria Chloroplast Nucleus Vacuole

49 Membrane Lipids Amphipathic Molecules, most of which spontaneously form bilayers Lipid that is, fatty molecules constitute about 50% of the mass of most animal cell membranes, nearly all of the remainder being protein. There are approximately lipid molecules in a 1 mm 1 mm area of lipid bilayer, or about 10 9 lipid molecules in the plasma membrane of a small animal cell. All of the lipid molecules in cell membranes are amphipathic (or amphiphilic) that is, they have a hydrophilic ("water-loving") or polar end and a hydrophobic ("water-fearing") or nonpolar end.

50 It is the shape and amphipathic nature of the lipid molecules that cause them to form bilayers spontaneously in aqueous environments. Hydrophilic molecules dissolve readily in water because they contain charged groups or uncharged polar groups that can form either favorable electrostatic interactions or hydrogen bonds with water molecules. Hydrophobic molecules, by contrast, are insoluble in water because all, or almost all, of their atoms are uncharged and nonpolar and therefore cannot form energetically favorable interactions with water molecules.

51 If dispersed in water, they force the adjacent water molecules to reorganize into ice like cages that surround the hydrophobic molecule. Because these cage structures are more ordered than the surrounding water, their formation increases the free energy. This free energy cost is minimized, however, if the hydrophobic molecules (or the hydrophobic portions of amphipathic molecules) cluster together so that the smallest number of water molecules is affected.

52 Membrane Lipids A typical biomembrane is assembled from Phosphoglycerides, Sphingolipids, and Steroids.

53 PHOSPHOLIPID BILAYERS One structure that can result when phospholipids are suspended in water is shown below. A bilayer of phospholipids forms a sphere in which water is trapped inside. The hydrophilic phosphate regions interact with the water inside and outside of the sphere. The fatty acids of the phospholipids interact and form a hydrophobic center of the bilayer.

54 Phosphoglycerides, the most abundant class of lipids in most membranes, are derivatives of glycerol 3-phosphate A typical phosphoglyceride molecule consists of a hydrophobic tail composed of two fatty acyl chains esterified to the two hydroxyl groups in glycerol phosphate and a polar head group attached to the phosphate group. The two fatty acyl chains may differ in the number of carbons that they contain (commonly 16 or 18) and their degree of saturation (0, 1, or 2 double bonds).

55 Classification of Phosphoglycerides Classified according to the nature of its head group. In phosphatidylcholines, the most abundant phospholipids in the plasma membrane, the head group consists of choline, a positively charged alcohol, esterified to the negatively charged phosphate. In other phosphoglycerides, an OH-containing molecule such as ethanolamine, serine, and the sugar derivative inositol is linked to the phosphate group. The plasmalogens are a group of phosphoglycerides that contain one fatty acyl chain, attached to glycerol by an ester linkage, and one long hydrocarbon chain, attached to glycerol by an ether linkage (COOOC). These molecules constitute about 20 percent of the total phosphoglyceride content in humans. Their abundance varies among tissues and species but is especially high in human brain and heart tissue.

56 Membrane lipids 1. Phospholipids Membrane Lipids Deformable (locomotion, cell division) Facilitate fusion or splitting of membranes

57 The parts of a phospholipid molecule phosphatidylcholine

58 A small tear in the bilayer creates a free edge with water; because this is energetically unfavorable, the lipids spontaneously rearrange to eliminate the free edge. (In eukaryotic plasma membranes, larger tears are repaired by the fusion of intracellular vesicles.) The prohibition against free edges has a profound consequence: the only way for a bilayer to avoid having edges is by closing in on itself and forming a sealed compartment. This remarkable behavior, fundamental to the creation of a living cell, follows directly from the shape and amphipathic nature of the phospholipid molecule.

59 Phospholipid motility (The types of movements possible for phospholipid molecules in lipid bilayer)

60 Fluidity of membrane

61 Sphingolipids Derived from sphingosine, an amino alcohol with a long hydrocarbon chain, and contain a long-chain fatty acid attached to the sphingosine amino group. In sphingomyelin, the most abundant sphingolipid, phosphocholine is attached to the terminal hydroxyl group of sphingosine. Thus sphingomyelin is a phospholipid, and its overall structure is quite similar to that of phosphatidylcholine. Other sphingolipids are amphipathic glycolipids whose polar head groups are sugars. Glucosylcerebroside, the simplest glycosphingolipid, contains a single glucose unit attached to sphingosine. In the complex glycosphingolipids called gangliosides, one or two branched sugar chains containing sialic acid groups are attached to sphingosine. Glycolipids constitute 2 10 percent of the total lipid in plasma membranes; they are most abundant in nervous tissue.

62 Cholesterol Cholesterol and its derivatives constitute the third important class of membrane lipids, the steroids. The basic structure of steroids is a four-ring hydrocarbon. Although cholesterol is almost entirely hydrocarbon in composition, it is amphipathic because its hydroxyl group can interact with water. Cholesterol is especially abundant in the plasma membranes of mammalian cells but is absent from most prokaryotic cells.

63 Cholesterol A) Formula B) Schematic drawing C) Space-filling model

64 (a) Cholesterol in a lipid bilayer a) In one layer of lipid bilayer b) In lipid bilayer (b)

65 As much as percent of the lipids in plant plasma membranes consist of certain steroids unique to plants. At neutral ph, some phosphoglycerides (e.g., phosphatidylcholine and phosphatidyl ethanolamine) carry no net electric charge, whereas others (e.g., phosphatidylinositol and phosphatidylserine) carry a single net negative charge. Nonetheless, the polar head groups in all phospholipids can pack together into the characteristic bilayer structure. Sphingomyelins are similar in shape to phosphoglycerides and can form mixed bilayers with them. Cholesterol and other steroids are too hydrophobic to form a bilayer structure unless they are mixed with phospholipids.

66 Three classes of membrane lipids

67 Four major phospholipids in mammalian plasma membranes. Different head groups are attached with the phosphate head in the lipid bilayer

68 The asymmetrical distribution of phospholipids and glycolipids in the lipid bilayer of human red blood cells.

69 Membranes are Asymmetric Lateral Asymmetry of Lipids: Lipids can cluster in the plane of the membrane - they are not uniformly distributed Transverse asymmetry of lipids In most cell membranes, the composition of the outer monolayer is quite different from that of the inner monolayer

70 Lipid Composition Influences the Physical Properties of Membranes A typical cell contains myriad types of membranes, each with unique properties bestowed by its particular mix of lipids and proteins. Several phenomena contribute to these differences. For instance, differences between membranes in the endoplasmic reticulum (ER) and the Golgi are largely explained by the fact that phospholipids are synthesized in the ER, whereas sphingolipids are synthesized in the Golgi. The proportion of sphingomyelin as a percentage of total membrane lipid phosphorus is about six times as high in Golgi membranes as it is in ER membranes. In other cases, the translocation of membranes from one cellular compartment to another can selectively enrich membranes in certain lipids.

71 Differences in lipid composition may also correspond to specialization of membrane function. For example, the plasma membrane of absorptive epithelial cells lining the intestine exhibits two distinct regions: apical surface faces the lumen of the gut and is exposed to widely varying external conditions; basolateral surface interacts with other epithelial cells and with underlying extracellular structures. In these polarized cells, the ratio of sphingolipid to phosphoglyceride to cholesterol in the basolateral membrane is 0.5:1.5:1, roughly equivalent to that in the plasma membrane of a typical unpolarized cell subjected to mild stress. In contrast, the apical membrane of intestinal cells, which is subjected to considerable stress, exhibits a 1:1:1 ratio of these lipids. The relatively high concentration of sphingolipid in this membrane may increase its stability

72 Membranes contain specialized lipids and proteins Proteins 30-70% Phospholipids 7-40% Sterols 0-25% Specialized membranes More than 90% Rhodopsin in photoreceptor disc membrane Protein rich mitochondrial membranes Transport optimized Red Blood Cell membrane