Location, structure Molecular components

Function

第二篇 细胞的结构与功能

Life activity of cell and life phenomena To be simplified: birth, aging, illness and deathIncluding: cell differentiation, growth and division, mobility, inheritance and mutation, metabolisms in energy and material, response tostimuli from outside the cell, cell senescence and death.具体说包括细胞的分化、生长与分裂、细胞的运动、遗传与变异、细胞的物质与能量代谢、细胞对外界刺激的应答、细胞的衰老与死亡。

Cellular structures and their functions

Part II Cellular structure and their functions

Cell membrane and transmembrane transportation

Endomembrane system and vesicle transport

Mitochondria and energy transformation

Nuclei

Cytoskeleton and cell movement

Cell junctions and cell adhesion

Extracellular matrix and its functions

Chapter 4. Cell membrane and transmembrane transportation

Chemical components of membrane

Across membrane transport of small molecules

Across membrane transport of large moleculesand particles

Cell surface and its specified structure

Abnormality of cell membrane and diseases

Cell membrane

Section 1. Chemical components of cellMembrane and their molecular structure

1.Chemical components of cell membrane

（ 1 ） lipids constitute the skeleton of the membrane

膜脂（ membrane lipid ）

phospholipids

cholesterol

glycolipid

Section 1. Chemical components of cellMembrane and their molecular structure

1.Chemical components of cell membrane

（ 1 ） lipids constitute the skeleton of the membrane

膜脂（ membrane lipid ）

phospholipids

cholesterol

glycolipid

Figure 10-3 Molecular Biology of the Cell (© Garland Science 2008)

PE PS PC

Figure 10-3 Molecular Biology of the Cell (© Garland Science 2008)

PE PS PC

Figure 10-3 Molecular Biology of the Cell (© Garland Science 2008)

PE PS PC

Figure 10-3 Molecular Biology of the Cell (© Garland Science 2008)

PE PS PC

Figure 10-18 Molecular Biology of the Cell (© Garland Science 2008)

Figure 10-4 Molecular Biology of the Cell (© Garland Science 2008)

Membrane lipid

phospholipids ： basic components ， 50%

Cholesterol :stabilize membrane structure and modulate the fluidity of membrane

glycolipid ： 5% or less ， located outer layer of membrane

Figure 10-5 Molecular Biology of the Cell (© Garland Science 2008)

Figure 10-3. A lipid micelle and a lipid bilayer seen in cross-section. Lipid molecules form such structures spontaneously in water. The shape of the lipid molecule determines which of these structures is formed. Wedge-shaped lipid molecules (above) form micelles, whereas cylinder-shaped phospholipid molecules (below) form bilayers.

Figure 10-11 Molecular Biology of the Cell (© Garland Science 2008)

Figure 10-12 Molecular Biology of the Cell (© Garland Science 2008)

The importance of the lipid bilayer

• The lipids of a membrane are more than simple structural elements:

• It is a skeleton of the membrane • Lipid composition can determine the physical

state of the membrane and influence the activity of particular membrane proteins.

• Membrane lipids also provide the precursors for highly active chemical messengers that regulate cellular function.

Figure 10-1c Molecular Biology of the Cell (© Garland Science 2008)

（ 2 ） membrane protein accomplish a lot of important membrane functions

MembraneProteins

内在膜蛋白（ intrinsic membrane protein ）整合膜蛋白（ integral membrane protein ）

外在膜蛋白 (extrinsic membrane protein)

脂锚定蛋白（ lipid anchored protein)

外周蛋白（ peripheral protein ）

脂连接蛋白（ lipid-linked protein ）

（ 3 ） sugar-chains from glycoproteins and Glycolipids cover the cell surface

2. Characteristics of the cell membrane

1. Asymmetry of lipids

2. Asymmetry of proteins

3. Asymmetry of sugar-chains

（ 1 ） membrane asymmetry

（ 2 ） Fluidity of the membrane guaranteed the biological functions of the membrane

1. Lipid layer is a two dimentaional fluid液晶态（ liquid-crystal state)

2. Membrane lipids have different movements

3. Many factors impacting the fluidity of the lipids

（ 1 ） the saturation of the fatty chain

（ 2 ） the length of the fatty chain

（ 3 ） cholesterol

（ 4 ） the ratio of phosphotidal choline(PC) and sphingomylin(SM)

（ 5 ） membrane proteins

相变温度的概念

T >phase-transition temperature, reducing fluidity

T <phase-transition temperatureIncreasing fluidity

4. The movement of lipid proteins

（ 1 ） lateral diffusion

（ 2 ） rotation

3. Molecular models of cell membrane

The pioneer researchers were E. Gorter and Grendel

（ 1 ） Sandwish modelTo account for permeability of membrane to non-lipid substances, Danielli and Davson proposed  sandwich model (later proved wrong) with phospholipid bilayer between layers of protein.

Blood ghost: red blood cell membrane

（ 2 ） unit membrane model

20C.C 50’s J.D Robertson

（三）流动镶嵌模型 fluid-mosaic model •  In 1972, Singer and Nicolson introduced the

currently accepted fluid-mosaic model of membrane structure.

• In this model, a flexible layer made of lipid molecules is interspersed with large protein molecules that act as channels, transporters through which other molecules enter and leave the cell. There are also receptors in the membrane. –  The core lipid bilayer exists in a fluid state, capable of

dynamic movement.– Membrane proteins form a mosaic of particles penetrating

the lipid to varying degree

The model described the fluidity and asymmetry of the membrane

1975 年 D.F Wallach 提出了一种“晶格镶嵌模型” （ crystal mosaic model)

1977 年 M.KJain 和 H.B White 又提出了“板块镶嵌模型”（ block mosaic model ）

（ 4 ） lipid raft （严格说，它不是模型而是一种特殊的结构）

Chaper 2 membrane transport of small molecules

1. Selective permeability and simple diffusion

2.Transport protein mediated transportation of small molecules

膜转运蛋白（ membrane transport protein ）

Carrier Protein

Channel Protein

（ 1 ） ion channels transporting various ions

Ion channel

Passive transport

Specificity for the ion size and charge

High speed of transporting , 106 to 108 /second

Conformation changes from opening to closing

K+ channel constitutively opens ，while most channels are gated opening

Figure 11-31 Molecular Biology of the Cell (© Garland Science 2008)

（ 1 ） carrier protein mediated facilitated diffusion

（ 3 ） carrier protein mediated positive transport

1. Ion pump hydrolyze ATP for active transport

钙泵

2. ion-driven cotransporters

cotransporters

symport antiport

ionion

Cotransport: coupled transport A special kind of active

transport• Two molecules travel together, one as a

passenger, the other as a driver. The driver diffuses down its electrochemical gradient, but it cannot do so unless it has the passenger.

• ATP is not directly involved, but it sets up the electrochemical gradient used to propel the driver.

• Symport•   The passenger and the driver are

transported in the same direction.

•   Na-glucose symport takes place in the intestine, from the gut lumen to the insides of the cells lining the gut.

glucose-Na symport

Naglucose

intestinal lining

• Antiport• The driver and passenger travel in

opposite directions.

Na+-H+ exchange carrierCl--HCO3

- exchanger

• The energy of ATP may be used directly or indirectly.

• Direct Active Transport. Some transporters bind ATP directly and use the

energy of its hydrolysis to drive active transport.

• Indirect Active Transport. Other transporters use the energy already stored in

the gradient of a directly-pumped ion. Direct active transport of the ion

establishes a concentration gradient. When this is relieved by facilitated

diffusion, the energy released can be harnessed to the pumping of some other

ion or molecule.

Chapter 3. membrane transport of big molecules and particles

Endocytosis

Exocytosis

1. Endocytosis

（ 1 ） phagocytosis 吞噬作用

Bacteria

A. Phagocytosis• Cell eating: cells engulf particles with

pseudopodia and pinches off a food vacuole.

• Two examples:

1. White Blood Cell

2. Amoeba

White Blood Cell

Bacteria

Phagocytosis: The uptake of large particles

Including: macromolecules, cell debris, even microorganisms and other cells.

Phagocytosis is usually restricted to specialized cells called Phagocytes.

Phagocytosis is initiated by cellular contact with an appropriate target.

Phagocytosis may be stimulated by the opsonins

Phagocytosis is driven by contractile activities of MF.

（ 2 ） Pinocytosis 胞饮作用

B. Pinocytosis

• Cell drinking: droplets of extracellular fluid are absorbed into the cell by small vesicles.

• Example:

Food Particles

（ 3 ） Receptor mediated endocytosis

C. Receptor-Mediated Endocytosis

• Importing specific macromolecules (hormones) into the cell by the inward budding of vesicles formed from coated pits (receptors).

Hormones

Receptors

Liver Cell

• In most animal cells, clathrin-coated pits and vesicles provide an efficient pathway for taking up specific macromolecules from the extracellular fluid. In this process the macromolecules bind to complementary transmembrane receptor proteins, accumulate in coated pits, and then enter the cell as receptor-macromolecule complexes in clathrin-coated vesicles.

• Receptor-mediated endocytosis provides a selective concentrating mechanism that increases the efficiency of internalization of particular ligands more than a hundredfold, so that even minor components of the extracellular fluid can be specifically taken up in large amounts without taking in a correspondingly large volume of extracellular fluid.

clathrin

2. Excytosis( 胞吐作用 )（一）结构性分泌途径（ constitutive secretion pathway)

（二）条件性分泌途径（ regulated secretion pathway)

Chapter4 .cell surface and specified structures

1. Cell coat or glycocalyx ( 细胞外被和胞质溶胶 )

2.Specified cell surface

1.Microvillus( 微绒毛 )

2. Cilia and flagella( 纤毛与鞭毛 )

3. 褶皱（ ruffe) 或片状伪足（ lamellipodium)

trachea

Chapter 5 membrane abnormality and diseases1. The abnormality of carrier protein and diseases1. 胱氨酸尿症（ cystinuria)

膜转运体异常疾病，遗传性

病人肾小管上皮转运胱氨酸及二氨基氨基酸（赖氨酸，精氨酸及鸟氨酸）的载体蛋白缺陷而 引起的疾病。

pH5-7 时，胱氨酸的饱和浓度为 0.3-0.4g/L

2. 肾性糖尿（ renal glycosuria)

2. Abnormality of ion channels and diseases

Cystic fibrosis ， CF

3. Abnormality of membrane receptor and diseases

(1). 家族性高胆固醇血症（ familial hypercholesterolemina)

(2). 重症肌无力（ myasthenia gravis)

自身免疫疾病， 体内产生了抗 N-Ach 受体的抗体。

2. 重症肌无力（ myasthenia gravis)

自身免疫疾病， 体内产生了抗 N-Ach 受体的抗体。

. Cancer and cell surface changes( 癌变和细胞表面的关系 )

（ 1 ） contact and grow inhibition loss 接触抑制丧失

（ 2 ） abnormality of membrane components( 细胞的组成异常 )

膜脂的改变： Gm3 Gd3

膜蛋白的改变

（ 3 ） surface antigen change 抗原性的改变

（ 4 ） the change of reactions with extracellular lectins( 与外源性凝集素的反应 )

Summery ：

Chemical components

model

Small molecule transport

Large molecule and particle transport

passive

active （载体介导运输）

Simple diffusion 自由扩散

Ion channels 离子通道

Carrier protein mediated facilitated diffusion 载体介导的易化扩散

Ion pump 离子泵

Cotransport 协同运输

symport

antiport

excytosis

endocytosis

phagocytosis

pinocytosis

Receptor mediated endocytosis

Cell surface ： 细胞外被（ cell coat ）或糖萼（ glycocalyx ）

Specified cell surface structure细胞表面的特化结构

microvillus

Cillia or flagella

Ruffle or lamellipodium

Cell membrane and diseases细胞膜与疾病