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

(鞭毛 )

(菌毛 )

Animal cells

Note: RBC has no inner cellular organelles

Plant cell

nuclear porenuclearenvelope

nucleous} nucleus

ribosomechloroplast

vacuole

mitochondrion

cytoplasmcell membrane

cell wall

ER

Golgi apparatus

Classification of Organelles(细胞器 )

● 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

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

(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

(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

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 O

2 (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

[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 （真菌） 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

肾

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

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

Typical concentration inside cell ~100 mM, d ~5 nm

Lattice model

N d 3=V

d=(V /N )1/3

=c−1 /3

Protein-protein inter-space

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

+, 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)

(分解代谢 )(合成代谢 )

(释能反应 )

● Amino acids (氨基酸 )– Basic structure

– Chirality: two isomeric

forms, called L-amino acids

and D-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

Large molecules● Lipid (脂类 )

– Character: amphiphilic (双亲的 ), (un)saturated

Saturated Unsaturated

Phosphatidylcholine(卵磷脂 )

~2

nm

~2

nm

胆碱

甘油骨架

– 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.

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component of plant cell walls

store energy

N

C

Right-handed

● Proteins

link: coils

N C

– Question: Does the primary structure determine secondary and tertiary structures?

– Functions: play roles in almost all movements of life

antibodies-antigen

Cell adhesions Ion channel

enzyme

substrates底物分子

enzyme

Enzyme-substratecomplex

nonsubstrate

product

Molecular machines(To be mentioned latter!)

The function of a protein is determined by its tertiary and quaternary structures!

抗原决定簇

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

(2位脱氧 )

– 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 (聚合酶 ). It

takes codons (密码子 ) 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!

胶束

● Cell membranes: fluid mosaic model [Singer & Nicolson (1972) Science]

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

DNA winds usually around in left handed

● Nuclear pore complex

[Nature 450 (2007) 695]

456 constituent proteins

molecular wight: ~50 MDa

§1.3 Molecular devices

Kinesin (驱动蛋白 )

hand-over-hand inchworm(尺蠖 )

1ATP

1ATP

dye

ADP [Science 303 (2004) 676]

[Cooper's book]

● Step: hand-over-hand is more possible

[Science 303 (2004) 676]

homework

Dynein (动力蛋白 )

(茎 ,柄 )

[Produce movement of Flagellum's filament]

Heavy chain

Tail

Light chain

Neck

Head

Myosin (肌球蛋白 )

● Structure

● Function: play role in muscle contraction

[structure]

[muscle contraction]

[work mechanism]

肌原纤维

肌节

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 )

Intermembrane space

Outer mitochondrialmembrane

Inner mitochondrialmembrane

Mitochondrial matrix

Outside mitochondrion

F1

Fo

[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

启动子

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 self-organized

– 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)