What is life? No exact answer However, life should have characters as

Transcription

1 What is life? No exact answer However, life should have characters as ability of self-organization ( 自我组织 ) ability of metabolism ( 新陈代谢 ) ability of response to stimulation ( 响应刺激 ) and self-regulation ( 自我调节 ) ability of growth and differentiation( 分化 ) ability of inheritance( 遗传 ) and reproduction( 繁殖 ) ability of evolution ( 进化 )

2 Lecture 1 Cells: the basic units of life Zhanchun Tu ( 涂展春 ) Department of Physics, BNU tuzc@bnu.edu.cn Homepage:

3 Main contents Cell physiology Survey of the molecules inside cells Molecular devices

4 2.1 Cell physiology

5 Size and morphology Size: several to tens of μm Various shapes (a) 5 cells of E. coli bacteria (b) 2 cells of yeast (c) Human red blood cell (d) Human white blood cell (e) Human sperm cell (f) Human epidermal (skin) cell (g) Human striated muscle cell (myofibril) (h) Human nerve cell?: can the size of cells be arbitrary large or small?

6 Function of Cells Like entire organisms, individual cells take in chemical or solar energy. Most of this energy gets discarded as heat, but a fraction turns into useful mechanical activity or the synthesis of other energy-storing molecules Each cell manufactures more of its own internal structure, in order to grow

7 Most cells can reproduce by mitosis( 有丝分裂 ) Cells must maintain a particular internal composition, sometimes in spite of widely varying external conditions Most cells maintain a resting electrical potential difference between their interiors and the outside world

8 Many cells move about, for example by crawling or swimming Cells can sense their internal and environmental conditions, and then do proper feedback Apoptosis( 凋亡 ): as an extreme form of feedback, a cell can even destroy itself.

9 Prokaryotes Include: Archaea and Bacteria Character ~1μm No specific nucleus No membrane enclosed subcellular organelles Double-layered membrane ( 纤毛 ) ( 鞭毛 )

10 Animal cells Note: RBC has no inner cellular organelles

11 Plant cell nuclear pore nuclear envelope Golgi apparatus nucleous ribosome ER } nucleus chloroplast vacuole mitochondrion cell wall cell membrane cytoplasm

12 Comparison Similarity Nucleus, cytoplasm, mitochondrion, cell membrane, Golgi apparatus, ER Difference Plant Cell Animal Cell With cell wall Without cell wall With chloroplast Without chloroplast Vacuole: large, at center Vacuole: small or absent Nucleus: beneath the cell wall Nucleus: at the center Larger size,regular shape Smaller size, irregular shape

13 Classification of Organelles Organelles that Process Information The Endomembrane System ER, Golgi apparatus, Lysosome Organelles that Process Energy Nucleus & Ribosome Mitochondrion, Chloroplast Others Peroxisome ( 过氧物酶体 ), Vacuoles, Cytoskeleton, Extracellular Structures

14 Nucleus

15 Functions The site of DNA duplication Store genes on chromatins Produce ribosomes in the nucleolus Produce messages (mrna) that code for proteins The site of genetic control of the cell's activities

16 Ribosome: machine making proteins 3 sites for trna binding (prokaryote) (eukaryote) S 表示沉降系数 不能进行简单的数学加和

17 ER: a complex factory

18 Functions of rough ER Segregates certain newly synthesized proteins away from the cytoplasm and transports them to other locations in cells Chemically modifies proteins in cells Functions of smooth ER Chemically modifies small molecules in cells Hydrolyzes glycogen ( 糖原 ) in animal cells Synthesizes lipids and steroids ( 类固醇 )

19 Golgi apparatus Transfer route ER Golgi Destinations Functions: (1) Receives proteins from the ER. (2) Concentrates, packages, and sorts proteins before they are sent to the destinations. (3) Synthesize polysaccharides ( 多聚糖 ) for the plant cell wall

20 Lysosome A lipid vesicle containing digestive enzymes ( 消化 酶) Size: ~1μm Function: hydrolyzes macromolecules proteins, polysaccharides ( 多聚糖 ), nucleic acids, and lipids into their monomers

21 Mitochondrion: energy transformer Size: d 1.5 μm, L=2-8 μm Structure Inner & outer membranes Crista, matrix Intermembrane space Functions Cells' power sources Produce ATP using fuel molecules and O2 (cellular respiration)

22 Chloroplast: site of photosynthesis Size: 3-8 μm Structure: Inner and outer membranes, thylakoid, stroma, granum Function: photosynthesis produces glucose

23 Peroxisome Both in animal and plant cells A lipid vesicle containing enzymes Size: μm Fucntion: Collect and broken down the toxic peroxides ( 过氧化物 )

24 Cytoskeleton Three types Microfilament Intermediate filament microtubule

25 Microfilament Stucture: Double-strand filaments consisting of G-actin monomer Function: Change cell shape and drive cellular motion Treadmilling effect [Pantaloni et al. (2001) Science] [Ananthakrishnan et al.(2007) Int J Biol Sci]

26 Intermediate filament Structure: tough, ropelike assemblage of fibrous proteins ( 纤维蛋白 ) Functions: resist tension stabilize cell's structure maintain cell's shape maintain the positions cellular organelles in cells

27 Microtubule Structure: Long, hollow cylinders of tubulin proteins + Functions: Rigid internal skeleton for some cells ( 肌球蛋白马达 ) Track for the movement of molecular motor Essential in distributing chromosomes during cell division ( 驱动蛋白马达 ) -

28 Extracellular Structures Cell wall (plant) Semirigid structure consisting of cellulose ( 纤维素 ) fibers Functions Supports for the cell and limits its volume Barrier to infections by fungi and other organisms Plasmodesmata ( 胞间连丝 ): plasma membrane-lined channels

29 Extracellular matrix (Animal) ( 蛋白多糖 ) ( 胶原质 ) Functions: holds cells together in tissues contributes to the physical properties of cartilage ( 软骨 ), skin, and other tissues filters materials passing between different tissues orients cell movements during embryonic development plays a role in chemical signaling from one cell to another

30 Core flow chart of a cell as a factory Cell membrane: receive signals ( order form ) Skeleton (and signal molecules) transfer the order form to cell nucleus ( head office ) Cell nucleus: make the producing scheme Ribosome: make primary products in terms of the scheme ER & Golgi: further make end products Skeleton & molecular motors transport end products to the destination Mitochondrion: "power plant" provides energy

31 2.2 Survey of molecules inside cells

32 The Periodic Table

33 Classifications of molecules in cells Small molecules Ions, water Sugars, bases, amino acids Big molecules Lipid, polysaccharides Proteins, DNA, RNA Macromolecular assemblies Lipid structures, cell membrane Chromosome, nuclear pore complex

34 Small molecules Ions Cations: H+, Na+, K+, Cu+, Cu2+, Ca2+, Mg2+, Fe2+, Fe3+ Anions: Cl- Complex ions: OH-, NH4+, SO42, PO43, HPO42 (Pi) Water (70% weight in cells) ε=81 Hydrophilic: polar groups Hydrophobic: nonpolar groups

35 Simple sugars: (CH2O)n Function: act as a source of energy by body tissues Glucose ( 葡萄糖 ) Note: Ring form predominates in cells Three-carbon sugar Pentose ( 戊糖 ) ( 核糖 ) ( 脱氧核糖 ) (In RNA) (In DNA) ( 甘油醛 )

36 Bases ( 碱基 ): A-T,G-C in DNA; A-U,G-C in RNA ( 嘧啶 ) 胞嘧啶 尿嘧啶 胸腺嘧啶 ( 嘌呤 ) 腺嘌呤 鸟嘌呤

37 Nucleotides ( 核苷酸 ) Basic structure 核苷 Functions building blocks of nucleic acids energy element of biochemical reactions in cells consist of AMP, ADP, ATP, GMP, GDP, GTP, etc. 核苷酸

38 ATP( 腺苷三磷酸 ), ADP( 腺苷二磷酸 ), AMP( 腺苷酸 ) Structure Synthesis and Hydrolysis + H2O Energy=7.3 kcal/mol=12 kbtr (in standard condition) Energy=12 kcal/mol=20 kbtr (in physiological condition)

39 Amino acids ( 氨基酸 ) Basic structure Chirality: two isomeric forms, called D-amino acids and L-amino acids. A puzzle? Only L-amino acids are commonly found in most organisms in the earth!

40 Twenty amino acids in Nature with charged hydrophilic side chains 天冬氨酸 精氨酸 组氨酸 赖氨酸 谷氨酸

41 with polar uncharged hydrophilic side chains 丝氨酸 苏氨酸 天冬酰胺酸 谷酰胺酸 酪氨酸 special cases Note: Gly is achiral 半胱氨酸 甘氨酸 脯氨酸

42 with nonpolar hydrophobic side chains 蛋氨酸 亮氨酸 异亮氨酸 丙胺酸 苯丙氨酸 色氨酸 缬氨酸

43 Peptide ( 肽, 缩氨酸 ) Polypeptide( 多肽 ): the primary structure of a protein

44 Big molecules Lipid ( 脂类 ) Character: amphiphilic ( 双亲的 ), (un)saturated ~2 nm ~2 nm Phosphatidylcholine ( 卵磷脂 ) Saturated Unsaturated

45 Typical lipids Phospholipids: Phosphatidylcholine, etc. Triglycerides ( 甘油三酸酯 ): fats and oils Steroids ( 类固醇 ): Cholesterol, Vitamin D2, etc. Sphingolipids ( 鞘脂 ): Sphingomyelin( 鞘磷脂 ), etc. Cholesterol Head group can be replaced with the other saturated chain triglyceride Vitamin D2 Sphingomyelin

46 Functions Fats and oils store energy Carotenoids( 类胡罗卜素 ) help plants capture light energy Steroids play regulatory roles Some lipids are vitamins (A, D, E, K) Phospholipids, Sphingolipids, Steroids: key components of cell membranes 磷脂酰乙醇胺 磷脂酰丝氨酸 糖酯

47 Polysaccharides ( 多聚糖 ) component of 纤维素 plant cell walls 纤 维 素 淀粉 糖原 store energy

48 Proteins C N Right-handed link: coils

49 Question: Does the primary structure determine secondary and tertiary structures? Functions: play roles in almost all movements of life product enzyme substrates 酶作用物 nonsubstrate The function of a protein is determined by its tertiary and quaternary structures! Enzyme-substrate complex enzyme Cell adhesions antibodies Ion channel Molecular machines (To be mentioned latter!)

50 DNA (double-stranded) & RNA (single-stranded)

51 DNA: double helix 10bp/pitch 11bp/pitch 12bp/pitch A-form Z-form (right-handed) (left-handed) B-form (right-handed)

52 RNA: mrna( 信使 -), trna( 转运 -), rrna( 核糖体 -) mrna: transcribed from DNA by RNA polymerase. It takes codons that determine amino acids 非翻译区 非翻译区 多聚 A 尾 Stabilize mrna Related to correctly start to synthesize proteins 7- 甲基鸟苷

53 trna: tertiary structure Secondary structure: cloverleaf shape Amino acid attachment site (always CCA) 3' 5' pair-backbone representation space-filling representation 5' OH 3' Hydrogen bonds between pairs Amino acid attachment site (always CCA) The anticodon, composed of the three bases that interact with mrna Pairs: A-U,G-C; G-U (few) Each type of amino acid has its own type of trna Sequences determine structures!

54 rrna: a component of ribosomes. Include 5S-,5.8S-,16S-,18S-,23S-,28S-rRNA Function: catalyze the assembly of amino acids into protein chains Human 5s rrna [Biochem. J. 371 (2003) 641]

55 Macromolecular assemblies Lipid structures micelle 胶囊 bilayer lipid molecule vesicle Liquid crystal phase. Cannot endure shear strain! hexagonal phase

56 Cell membranes: fluid mosaic model [Singer & Nicolson 1972] 糖蛋白 Composite membrane, can endure shear strain!

57 Chromosome 组蛋白 11nm 核小体 细胞分裂 中期染色体

58 Nuclear pore complex 456 constituent proteins molecular wight: ~50 MDa [Nature 450 (2007) 695]

59 2.3 Molecular devices

60 Kinesin hand-over-hand inchworm( 尺蠖 ) [Cooper's book] 1ATP 1ATP dye ADP [Science 303 (2004) 676]

61 Step: hand-over-hand is more possible [Science 303 (2004) 676]

62 Dynein [Produce movement of Flagellum's filament] (茎,柄)

63 Myosin Structure Light chain [structure] Tail Heavy chain Neck Head Function: play role in muscle contraction [muscle contraction] 肌原 纤维 [work mechanism]

64 Ion channels Passive transport (diffusion, spontaneous)

65 Active transport (cost energy)

66 Example 1: Na+-K+ pump Primary active transport with the direct aid of ATP

67 Example 2: Secondary active transport not use ATP directly; energy comes form ion concentration gradient established by primary active transport

68 ATP synthase ( 合成酶 ) Outside mitochondrion Outer mitochondrial membrane g Intermembrane space a b a b b a F0 F1 [work] Inner mitochondrial membrane Mitochondrial matrix

69 Flagellum( 鞭毛 ) 钩 55nm 推进器 衬套 16nm Peptidoglycan( 肽聚糖 ) 螺栓 41nm Energy source: electrochemical gradient between membranes

70 DNA polymerase ( 聚合酶 ) (hand-like) A machine for DNA replication

71 RNA polymerase a special sequence of DNA to which RNA polymerase binds very tightly A machine that transcribe DNA to RNA

72 Ribosome: machine making proteins

73 . Summary & further reading

74 Summary Cell's classification Prokaryote (Archaea and Bacteria) Eukaryote (animal, plant, fungus 真菌 ) Cellular organelles and their functions Nucleus, ribosome, cytoplasm, mitochondrion, chloroplast, cell membrane, Golgi apparatus, ER,...

75

76 Constituent molecules Small: ions, water, sugars, bases, amino acids Big: lipid, polysaccharide, proteins, DNA, RNA Macromolecular assemblies: Lipid structures, cell membrane, chromosome Molecular devices Motor proteins: Kinesin, Dynein, Myosin Ion channels and pumps Rotation motor: ATP synthase, flagellum motor DNA polymerase, RNA polymerase, ribosome

77 A wonderful and active world inside cells Full of puzzles Is the size of cells arbitrary small or large? Which factors determine the shape of cells? How and why mrna penetrate the nuclear pores? How and why RNA and proteins fold? Why and how can macromolecular assemblies selforganized What is the mechanism of molecular devices? How energy and information flow in cells?...

78 Further reading W. K. Purves, D. Sadava, G. H. Orians, and H. Craig Heller, Life: The Science of Biology (W. H. Freeman & Com, 2007) B. Alberts, A. Johnson, J. Lewis, M. Raff, K. Roberts, and P. Walter, Molecular Biology of the Cell (Garland Science, 2002)