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1 Syllabus ( Instructors: (Tai-Huang Huang ) & (Chi-Ming Chen) ( ) ; bmthh@ibms.sinica.edu.tw Web site: Reference books: (, 316 ) "Cell and Molecular Biology -- Concepts and Experiments" by Karp "Biophysics -- An Introduction" by Rodney Cotterill Part I: Introduction to Cell Biology (T.-h. Huang). 9/12 Structures of Cells Karp Chap.1 9/19 The Chemical Basis of Life Karp Chap. 2 9/26 Bioenergetics, Enzymes, and Metabolism Karp Chap. 3 10/3 The Nature of the Gene and the Genome Karp Chap /17 Cellular Reproduction Karp 14 10/24 The Immune response Karp Chap /31 Quiz (1 hour) Course

2 What is biophysics? Use of physical methods to investigate biological phenomena. Advanced physical techniques NMR, X-ray crystallography, optical spectroscopy, microscopy, calorimeter etc. Advanced physical concepts Computational techniues, theoretical analysis.

3 [About the Cover] Other Issues: Contents: Volume 85, Issue 3, September 2003 [Index by Author] BIOPHYSICAL THEORY AND MODELING CHANNELS, RECEPTORS, AND TRANSPORTERS MEMBRANES MUSCLE AND CONTRACTILITY NUCLEIC ACIDS PHOTOBIOPHYSICS PROTEINS SUPRAMOLECULAR ASSEMBLIES SPECTROSCOPY, IMAGING, OTHER TECHNIQUES CELL BIOPHYSICS BIOENERGETICS CORRECTIONS

4 BIOPHYSICAL THEORY AND MODELING: Bacterial Flagellar Microhydrodynamics: Laminar Flow over Complex Flagellar Filaments, Analog Archimedean Screws and Cylinders, and Its Perturbations Mathematical Model of the Spatio-Temporal Dynamics of Second Messengers in Vi Transduction Molecular Dynamics Simulation of Surfactin Molecules at the Water-Hexane Inter A Model of Calcium Waves in Pancreatic and Parotid Acinar Cells Concerted Simulations Reveal How Peroxidase Compound III Formation Results in Cellular Oscillations Vibrational Frequency Shifts and Relaxation Rates for a Selected Vibrational Mod in Cytochrome c Molecular Dynamics Simulation of Bacteriorhodopsin's Photoisomerization Using Ab Initio Forces for the Excited Chromophore. Charge Distribution in 7-Methylguanine Regarding Cation- Interaction with Protei Factor eif4e Two-State Folding over a Weak Free-Energy Barrier Thermodynamics of - and ß-Structure Formation in Proteins Conformational Dynamics of the F 1 -ATPase ß-Subunit: A Molecular Dynamics Stud A Tree-Based Algorithm for Determining the Effects of Solvation on the Structu of Salivary Gland Tripeptide NH 3+ -D-PHE-D-GLU-GLY-COO - Similarity of Force-Induced Unfolding of Apomyoglobin to Its Chemical-Induced Unfolding: An Atomistic Molecular Dynamics Simulation Approach

5 What is Life and how do you define a living system? 1. Self sustain 2. Ability to propagate Cell is the smallest living system. What is Cell How does cell function? How does cell propagate? 1. The Evolution of Cells

6 (Chemical Evolution) (prebiotic soup) - Reducing atmosphere: N 2, CO 2, H 2 O, H 2, CH 4, NH 3, H 2 S amino acids nucleic acids proteins cells - O 2 appeared in 2.5 billion years ago : Photosynthesis ( ) Miller Urey experiment: Subject above compounds in a right temperatures and lightening conditions to produce: amino acids (four), urea, HCN and adenine

8 (Self Organization) (Biological Evolution) -

9 RNA 5. 6.

10 (prokaryotic cells) (eukaryotic cells)

12 (The Cell Theory) (organism) (metabolism) (heredity)

13 II. Basic Properties of Cells: Cells are: Highly complex and organized. Possess a genetic program and the means to use it. Capable of producing more of themselves. Acquire and utilize energy. Carry out a variety of chemical reactions. Engage in numerous mechanical activities. Able to respond to stimuli. Capable of self-regulations. Cells are the smallest unit to exhibit life phenomenon. Immotalized cells (Cell line): Hela cell

14 Cell 1. The Evolution of Cells 2. Prokaryotes vs. Eukaryotes

15 Bacteria 2. Prokaryotes ( ) vs. Eukaryotes ( ) Plants Animals 3. Organelles ( )

16 Different types of human cells

17 Relative sizes of cells and cell components

18 Levels of cellular molecular organization

19 (prokaryotic cells) (eukaryotic cells) (membrane) DNA (ribosome) DNA

21 (bacteria) Carl Woese Archaebacteria Eubacteria

22 The Structure of Prokaryotic Cells: 1. Cell wall: Made of a single peptidoglycan. Gram-positive bacteria: Thick cell wall. Gram-negative bacteria: Thin cell wall. 2. Plasma Membrane: Lipid bilayer w/protein embedded. 3. Flagellum: Proteins that allow cells to move around.

23 Plant cell:

25 (eukaryotic cells)

27 The Structure of Eukaryotic Cells: I. External framework. 1. Plasma membrane: fluid mosaic model consists of proteins embedded in lipid bilayers. The proteins (peripheral or integral) may have protein, peptide or carbohydrate attached to them. 2. Cytoskeleton: - Microfilaments: Thre3ads of 3-6 nm thick that are compound of two proteins, actin and myosin, and are capable of contraction - Microtubules: Cylinders of nm thick protein, tubulia, wound in a spiral shape, microtubules radiate outward from a central region in the interior of the cell in three dimension. Microtubules are not stable components, but constantly undergoing assembly and disassembly.

28 (Membranes) Biological membranes are organized assemblies of lipids and proteins with small amounts of carbohydrates. Yet they are not impermeable barriers to the passage of materials. Rather, they regulate the composition of the intracellular medium by controlling the flow of nutrients, waste products, ions, etc., into and out of the cell.

29 Skeleton ( )

30 II. Internal Components: (1). Endoplasmic Reticulum (ER) The extensive system of internal membranes that exists within the cells of eukaryotic cells. Provide channels through the interior of the cell (Rough ER). 2. Provides a site for enzymes. (Membrane proteins, smooth ER). 3. Creates subcompartment within the cell [Fusion of m.b. to form various cisternae (Vesicles)].

31 (Endoplasmic Reticulum) (rough ER) (smooth ER) (enzyme)

32 (Ribosome) mrna

33 (2). The Nucleus: A semipermanent vesicle derived from ER, which contains the cell s hereditary apparatus and isolates it from the rest of the cell. It composes of: The Nuclear envelope: An encircling system of double membrane which defines the boundary of the nucleus. - Nculear pores: Shallow depressions on the envelope (50-80 nm apart), embedded with protein channels for passage of proteins and RNAs. 2. The nucleoplasm: The cell substance enclosed by thenuclear envelope (contains no ribosomesome) 3. Chromosomes: The DNA of eukaryotic cells are fragmented into several segments, each complexed with proteins. - Chromosomes of eukaryotic cells can be condensed into compact rods for ready movement during cell division and later unraveled and can no longer be distinguished individually with a light microscope. 4. Nucleolus: A dark region in the nucleus where very active rrna (ribosomal synthesis is taking place)

34 (Nucleus) DNA

35 (chromatin) (chromosome) DNA RNA (nucleoli) RNA (ribosomal RNA or rrna) (nuclear envelope) (ER) 50 80nm RNA

36 (Golgi Appartus)

38 (3). The Golgi Complex (Aparatus) : A collection of Golgi bodies which are flattened stacks of membrane derived from E.R. - Function in the collection, packaging, and distribution of molecules synthesized elsewhere in the cell (Cell delivery system). Advantages: - They provide exist for the cells. - They facilitate growth of the cell - They isolate certain enzymes within cacs (microbodies). (4) Microbodies: (1). Lysosomes: Vesicles that contain in a concentrates mixture digestive enzymes of the cell. (lipases, proteases, lysozymes, nucleases) (2). Peroxisome: Vesicles containing oxidative enzymes. (3). Glyoxysomes: Vesicles containing enzymes for converting fat into carbohydrates, present only in plants.

39 (Lysosome)

40 (5). Relict Symbions: : (1). Mitochondria Microbodies (Not derived from ER): 1. Long tubular shape of 1-3 microns. 2. Bounded by two membrane, the outer m.b. is similar to plasma m.b., the inner m.b. folds into lamellae which partition the mitochondria into Cristae, 3. Mitochondria is cell Power plant and is the site of aerobic respiration (Oxidative phosphorylation) to produce ATP. 4. It maintains a circular DNA, encoding proteins and small RNA and robosomal components for producing essential proteins. 5. Mitochondria is capable of undergo division to produce new mictochondria. Most of the components required to assemble a new mitochondria are encoded as genes within the eukaryotic nucleus. (2). Chloroplasts ( ): The plant equivalent of mitochondria. It contains chlorophyl ( ).

41 (Mitochondria) (chloroplasts) µm 7 µm

42 DNA..

43 Plant cell:

44 A comparison of prokaryotic and Eukaryotic Cells: (1). Features held in common by the two types of cell: 1. Plasma membrnane of similar construction. 2. Genetic information encoded in DNA using identical genetic code. 3. Similar mechanisms for transcription and translation of genetic information, including similar ribosomes. 4. Shared apparatus for conservation of chemical energy as ATP (located in plasma membrane of prokaryotes and the mitochondria membrane of eukaryotes). 5. Similar mechanism for synthesizing and inserting membrane proteins. 6. Proteosomes (protein digesting structures) of similar construction (between archaebacteria and eukaryotes)

45 (2). Features of eukaryotic cells not found in prokaryotes: 1. Division of cells into nucleus and cytoplasm, separated by a nuclear envelope containing complex pore structures. 2. Complex chromosomes composed of DNA and associated proteins that are capable of compacting into mitotic structure 3. Complex membraneous cytoplasmic organelles (includes endoplasmic reticulum, Golgi complex.. Etc). 4. Specialized cytoplasmic organelles for aerobic respiration (mitochondria) and photosynthesis (Chloroplasts). 5. Complex cytoskeletal system. 6. Complex flagella and cilia. 7. Capable of ingesting fluid and particulate material by enclosur within plasma membrane vesicles (endocytosis and phagocytosi 8. Cellulose-containing fluid walls (in plant). 9. Cell division utilizing a microtubule-containing mitotic spindle that separate chromosomes. 10. Presence of two copies of genes per cell (diploidy), one from each parent. 11. Sexual reproduction requiring meiotic and fertilization.

46 Virus: Small oblitory intracellular parasites which cannot reproduce by themselves unless present within the host cells, which, depending on the specific virus, may be a plant, animal Or bacteriz cells. 1. Outside the cell viruses exist as virions. 2. Virions contain a small amount of genetic material which can be DNA (single or double stranded) or RNA. 3. The virion DNA or RNA may code for few to few hundreds of proteins. 4. The genetic material is surrounded by a protein capsule, or capsid, which is generally made up of a specificc number of subunits organized into a polyhedron. 5. Virions are molecular aggregates which by themselves are unable to reproduce, metobolize or carry out activities associated with life. 6. Most virus infect only specific types of hosts. 7. Modes of infections: (i) Taken over the host cell machinery leading to the death of host cell: (ii) Insert its DNA into host cell chromosomal DNA to become provius. Viroid: The simplest pathogents consisting of small circular RNA molecule that totally lack a protein coat.

47 AIDS

48 SARS

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untitled 1 1-1 1-3 1-2 2 (cell membrane) (cytoplasm) (organelles) 1-1 1-1 1-1 (Cell Membrane) 1972 (S. J. Singer) (G. L. Nicholson) (fluid-mosaic model) 1. 2. 1-2 3. 1 3 (phospholipids) 55% 25% (glycoproteins)