Download Document

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 1
Cells: the basic units of life
Zhanchun Tu ( 涂展春 )
Department of Physics, BNU
Email: tuzc@bnu.edu.cn
Homepage: www.tuzc.org
Main contents
●
Cell physiology
●
Survey of the molecules inside cells
●
Molecular devices
§1.1 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 ( 表皮 ) cell
(g) Human striated muscle ( 横纹肌 ) cell
(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 ( 原核生物 )
●
Include: Archaea and Bacteria
●
Character
–
~1μm
–
No specific nucleus
–
No membrane enclosed
subcellular organelles
–
Double-layered membrane
( 菌毛 )
( 鞭毛 )
Animal cells
Note: RBC has no inner cellular organelles
Plant cell
nuclear pore
nuclear
envelope
Golgi apparatus
nucleous
ribosome
ER
}
nucleus
chloroplast
vacuole
mitochondrion
cell wall
cell membrane
cytoplasm
Classification of Organelles( 细胞器 )
●
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
Nucleus
层状体
●
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
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
ER: a complex factory
( 胞腔 )
●
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 ( 水解 ) glycogen ( 糖原 ) in animal cells
–
Synthesizes lipids and steroids ( 类固醇 )
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
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
( 葡萄糖 )
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
[Pantaloni et al. (2001) Science]
[Ananthakrishnan et al.(2007) Int J Biol Sci]
●
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
( 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 )
-
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 （真
菌） and other organisms
Plasmodesmata ( 胞间连丝 ):
plasma membrane-lined channels
●
Extracellular matrix (Animal)
( 蛋白多糖 )
肾
( 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
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
Homework
§1.2 Survey of molecules
inside cells
The Periodic Table
Classifications of molecules in cells
●
●
●
Small molecules
–
Ions, water
–
Sugars, bases, amino acids
Large molecules
–
Lipid, polysaccharides
–
Proteins, DNA, RNA
Macromolecular assemblies
–
Lipid structures, cell membrane
–
Chromosome, nuclear pore complex
Crowding in cell
Protein-protein inter-space
Lattice model
3
N d =V
1/ 3
−1 /3
d =(V / N ) =c
Typical concentration inside cell ~100 mM, d ~5 nm
Size of protein ~ 3-5 nm
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
●
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 )
●
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
●
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
●
ATP( 腺苷三磷酸 ), ADP( 腺苷二磷酸 ), AMP( 腺苷酸 )
Structure
Synthesis and Hydrolysis
( 释能反应 )
( 分解代谢 )
( 合成代谢 )
+
H2O
Energy=7.3 kcal/mol=12 kBTr
(in standard condition)
Energy=12 kcal/mol=20 kBTr
(in physiological condition)
●
Amino acids ( 氨基酸 )
–
Basic structure
–
Chirality: two isomeric
forms, called L-amino acids
and D-amino acids.
A puzzle?
Only L-amino acids are
commonly found in most
organisms in the earth!
–
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
●
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
●
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
●
Peptide ( 肽 , 缩氨酸 )
Polypeptide( 多肽 ): the primary structure of a protein
Large molecules
●
Lipid ( 脂类 )
–
Character: amphiphilic ( 双亲的 ), (un)saturated
Phosphatidylcholine
( 卵磷脂 )
甘油骨架
~2 nm
~2 nm
胆碱
Saturated
Unsaturated
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
–
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 )
component of
纤维素 plant cell walls
淀粉
糖原
store energy
●
Proteins
N
C
C
N
Right-handed
link: coils
–
Question: Does the primary structure determine
secondary and tertiary structures?
–
Functions: play roles in almost all movements of life
product
enzyme
substrates
底物分子
nonsubstrate
The function of a protein is
determined by its tertiary
and quaternary structures!
Enzyme-substrate
complex
enzyme
抗原决定簇
Cell adhesions
antibodies-antigen
Ion channel
Molecular machines
(To be mentioned latter!)
●
DNA (double-stranded) & RNA (single-stranded)
(2 位脱氧 )
–
DNA: double helix
10bp/pitch
11bp/pitch
12bp/pitch
A-form
Z-form
(right-handed) (left-handed)
B-form (right-handed)
–
RNA: mRNA( 信使 -), tRNA( 转运 -), rRNA( 核糖体 -)
mRNA: transcribed from DNA by RNA polymerase ( 聚合酶 ). It
takes codons ( 密码子 ) 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
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!
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]
Macromolecular assemblies
●
Lipid structures
micelle
胶束
bilayer
lipid
molecule
vesicle
Liquid crystal phase.
Cannot endure shear strain!
hexagonal phase
●
Cell membranes: fluid mosaic model
[Singer & Nicolson (1972) Science]
糖蛋白
Composite membrane, can endure shear strain!
●
Chromosome
组蛋白
11nm
核小体
细胞分裂
中期染色体
DNA winds usually around in left handed
●
Nuclear pore complex
456 constituent proteins
molecular wight: ~50 MDa
[Nature 450 (2007) 695]
§1.3 Molecular devices
Kinesin ( 驱动蛋白 )
hand-over-hand
inchworm( 尺蠖 )
[Cooper's book]
1ATP
1ATP
dye
ADP
[Science 303 (2004) 676]
homework
●
Step: hand-over-hand is more possible
[Science 303 (2004) 676]
Dynein ( 动力蛋白 )
[Produce movement
of Flagellum's filament]
(茎,柄)
Myosin ( 肌球蛋白 )
●
Structure
Light chain
[structure]
Tail
Heavy chain
Neck
Head
●
Function: play role in muscle contraction
肌节
[muscle contraction]
肌原
纤维
[work mechanism]
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 transport
not use ATP directly;
energy comes form ion
concentration gradient
established by primary
active transport
ATP synthase ( 合成酶 )
F1
Mitochondrial matrix
Inner mitochondrial
membrane
Fo
Intermembrane space
Outer mitochondrial
membrane
[work]
Outside mitochondrion
Flagellum( 鞭毛 )
钩
55nm
推进器
衬套
16nm
Peptidoglycan( 肽聚糖 )
螺栓
41nm
Energy source: electrochemical gradient between membranes
DNA polymerase ( 聚合酶 )
(hand-like)
A machine for DNA replication
RNA polymerase
启动子
a special sequence of DNA
to which RNA polymerase
binds very tightly
A machine that transcribe DNA to RNA
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
–
Large: lipid, polysaccharide, proteins, DNA, RNA
–
Macromolecular assemblies: Lipid structures, cell
membrane, chromosome, nuclear pore complex
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 penetrates the nuclear pores?
–
How and why RNA and proteins fold?
–
Why and how can macromolecular assemblies selforganized
–
What is working 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)