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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 )
Lecture 1Cells: the basic units of life
Zhanchun Tu (涂展春 )
Department of Physics, BNU
Email: [email protected]
Homepage: www.tuzc.org
Main contents
● Cell physiology
● Survey of the molecules inside cells
● Molecular devices
§2.1 Cell physiology
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?
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
● 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
● 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.
Prokaryotes● Include: Archaea and Bacteria● Character
– ~1μm– No specific nucleus– No membrane enclosed
subcellular organelles– Double-layered membrane
(鞭毛 )
(纤毛 )
Animal cells
Note: RBC has no inner cellular organelles
Plant cellnuclear porenuclearenvelopenucleous
} nucleus
ribosomechloroplast
vacuole
mitochondrion
cytoplasmcell membrane
cell wall
ER
Golgi apparatus
Comparison
Plant Cell Animal Cell
With cell wall Without cell wall
With chloroplast Without chloroplast
Vacuole: large, at center Vacuole: small or absent
Larger size,regular shape Smaller size, irregular shape
Nucleus: beneath the cell wall Nucleus: at the center
● Similarity– Nucleus, cytoplasm, mitochondrion,
cell membrane, Golgi apparatus, ER
● Difference
Classification of Organelles● Organelles that Process Information
– Nucleus & Ribosome● The Endomembrane System
– ER, Golgi apparatus, Lysosome● Organelles that Process Energy
– Mitochondrion, Chloroplast● Others
– Peroxisome (过氧物酶体 ), Vacuoles, Cytoskeleton, Extracellular Structures
Nucleus
● 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
Ribosome: machine making proteins
(prokaryote)
(eukaryote)
3 sites for tRNA binding
S表示沉降系数,不能进行简单的数学加和
ER: a complex factory
● 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 )
Golgi apparatus
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
Transfer route
ER
Golgi
Destinations
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
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)
Chloroplast: site of photosynthesis
● Size: 3-8 μm● Structure: Inner and outer membranes,
thylakoid, stroma, granum● Function: photosynthesis produces glucose
Peroxisome
● Both in animal and plant cells
● A lipid vesicle containing enzymes
● Size: 0.2-1.7 μm● Fucntion: Collect and
broken down the toxic peroxides (过氧化物 )
Cytoskeleton● Three types
– Microfilament– Intermediate
filament– microtubule
● Microfilament– Stucture: Double-strand
filaments consisting of G-actin monomer
– Function: Change cell shape and drive cellular motion
– Treadmilling effect
[Ananthakrishnan et al.(2007) Int J Biol Sci][Pantaloni et al. (2001) Science]
● 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
● Microtubule– Structure: Long, hollow
cylinders of tubulin proteins– Functions:
● Rigid internal skeleton for some cells
● Track for the movement of molecular motor
● Essential in distributing chromosomes during cell division
(驱动蛋白马达 )
(肌球蛋白马达 )
+ -
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
(蛋白多糖 )
(胶原质 )
● Extracellular matrix (Animal)
– 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
Core flow chart of a cell as a factory
Cell membrane: receive signals (“order form”)
Skeleton (and signal molecules)
Cell nucleus: make the producing scheme
Ribosome: make primary products in terms of the scheme
ER & Golgi: further make end products
Skeleton & molecular motors
Mitochondrion: "power plant" provides energy
transfer the order form to cell nucleus (“head office”)
transport end products to the destination
§2.2 Survey of molecules
inside cells
The Periodic Table
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
Small molecules● Ions
– Cations: H+, Na+, K+, Cu+, Cu2+, Ca2+, Mg2+, Fe2+, Fe3+
– Anions: Cl-
– Complex ions: OH-, NH4
+, SO4
2–, PO4
3–, HPO4
2− (Pi)
● Water (70% weight in cells)
Hydrophilic: polar groups
Hydrophobic: nonpolar groups
ε=81
● Simple sugars: (CH2O)
n
Glucose(葡萄糖 )
Pentose(戊糖 )
(核糖 ) (脱氧核糖 )
(In RNA) (In DNA)
Three-carbon sugar
(甘油醛 )
Note: Ring form predominates in cells
Function: act as a source of energy by body tissues
● Bases (碱基 ): A-T,G-C in DNA; A-U,G-C in RNA
(嘧啶 )
(嘌呤 )
胞嘧啶 胸腺嘧啶 尿嘧啶
腺嘌呤 鸟嘌呤
● Nucleotides (核苷酸 )– Basic structure
– Functions● building blocks of nucleic acids● energy element of biochemical reactions in cells
– consist of● AMP, ADP, ATP, GMP, GDP, GTP, etc.
核苷 核苷酸
● ATP(腺苷三磷酸 ), ADP(腺苷二磷酸 ), AMP(腺苷酸 )
Structure
+ H2O
Synthesis and Hydrolysis
Energy=7.3 kcal/mol=12 kBT
r
Energy=12 kcal/mol=20 kBT
r
(in standard condition)
(in physiological condition)
● Amino acids (氨基酸 )– Basic structure
– Chirality: two isomeric
forms, called D-amino
acids and L-amino acids. Only L-amino acids are commonly found in most organisms in the earth!
A puzzle?
– Twenty amino acids in Nature
● with charged hydrophilic side chains
精氨酸 组氨酸 赖氨酸
天冬氨酸 谷氨酸
● with polar uncharged hydrophilic side chains
● special cases
丝氨酸 苏氨酸 天冬酰胺酸 谷酰胺酸 酪氨酸
半胱氨酸 甘氨酸 脯氨酸
Note: Gly is achiral
● with nonpolar hydrophobic side chains
丙胺酸 异亮氨酸 亮氨酸
蛋氨酸 苯丙氨酸 色氨酸 缬氨酸
● Peptide (肽 ,缩氨酸 )
Polypeptide( 多肽 ): the primary structure of a protein
Big molecules● Lipid (脂类 )
– Character: amphiphilic (双亲的 ), (un)saturated
Saturated Unsaturated
Phosphatidylcholine(卵磷脂 )
~2 n
m
~2 n
m
– Typical lipids● Phospholipids: Phosphatidylcholine, etc.● Triglycerides (甘油三酸酯 ): fats and oils● Steroids (类固醇 ): Cholesterol, Vitamin D
2, etc.
● Sphingolipids (鞘脂 ): Sphingomyelin(鞘磷脂 ), etc.
triglyceride
Cholesterol
Vitamin D2
SphingomyelinH
ead
grou
p
can be replaced with the other saturated chain
– 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
● Polysaccharides (多聚糖 )淀粉 糖原
纤维素
纤维素component of plant cell walls
store energy
N
C
Right-handed
● Proteins
link: coils
– Question: Does the primary structure determine secondary and tertiary structures?
– Functions: play roles in almost all movements of life
antibodies
Cell adhesions Ion channel
enzyme
substrates酶作用物
enzyme
Enzyme-substratecomplexnonsubstrate
product
Molecular machines(To be mentioned latter!)
The function of a protein is determined by its tertiary and quaternary structures!
● DNA (double-stranded) & RNA (single-stranded)
– DNA: double helix
B-form (right-handed)
A-form (right-handed)
Z-form(left-handed)
10bp/pitch 11bp/pitch 12bp/pitch
– 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
Stabilize mRNA
多聚 A尾
Related to correctly start to synthesize proteins
7-甲基鸟苷
tRNA:
Amino acidattachment site(always CCA) OH
5'
3'
Hydrogen bonds
between pairs
Pairs: A-U,G-C; G-U (few)
5'
3'
Amino acidattachment site(always CCA)
The anticodon, composed of the three bases that interact with mRNA
Secondary structure: cloverleaf shape
tertiary structure
space-filling representationpair-backbone representation
Sequences determine structures!
Each type of amino acid has its own type of tRNA
rRNA: a component of ribosomes. Include 5S-,5.8S-,16S-,18S-,23S-,28S-rRNA
[Biochem. J. 371 (2003) 641]Human 5s rRNA
Function: catalyze the assembly of amino acids into protein chains
Macromolecular assemblies● Lipid structures
lipidmolecule
micelle
bilayer
hexagonal phase
vesicle
Liquid crystal phase.Cannot endure shear strain!
胶囊
● Cell membranes: fluid mosaic model [Singer & Nicolson 1972]
Composite membrane, can endure shear strain!
糖蛋白
● Chromosome
组蛋白
核小体
11nm
细胞分裂中期染色体
● Nuclear pore complex
[Nature 450 (2007) 695]
456 constituent proteins
molecular wight: ~50 MDa
§2.3 Molecular devices
Kinesinhand-over-hand inchworm(尺蠖 )
1ATP
1ATPdye
ADP [Science 303 (2004) 676]
[Cooper's book]
● Step: hand-over-hand is more possible
[Science 303 (2004) 676]
Dynein
(茎 ,柄 )
[Produce movement of Flagellum's filament]
Heavy chain
Tail
Light chain
Neck
Head
Myosin● Structure
● Function: play role in muscle contraction
[structure]
[muscle contraction]
[work mechanism]
肌原纤维
Ion channels● Passive transport (diffusion, spontaneous)
● Active transport (cost energy)
● Example 1: Na+-K+ pump
Primary active transport with the direct aid of ATP
● Example 2: Secondary active transportnot use ATP directly; energy comes form ion concentration gradient established by primary active transport
ATP synthase (合成酶 )
Outer mitochondrialmembrane
Inner mitochondrialmembrane
Intermembrane space
Mitochondrial matrix
Outside mitochondrion
F1
F0
ab
g
aa
b
b
[work]
Flagellum(鞭毛 )
衬套
推进器
钩
螺栓
55nm
16nm
41nm
Energy source: electrochemical gradient between membranes
Peptidoglycan(肽聚糖 )
DNA polymerase (聚合酶 )
(hand-like)
A machine for DNA replication
RNA polymerase
A machine that transcribe DNA to RNA
a special sequence of DNA to which RNA polymerase binds very tightly
Ribosome: machine making proteins
§. Summary & further reading
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, ...
● 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
● 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 self-
organized– What is the mechanism of molecular devices?– How energy and information flow in cells? ...
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)