CHAPTER 4 Interactions Between Cells and Their Environment.

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1 CHAPTER 4 Interactions Between Cells and Their Environment

2 OUTLINE 4.1 CELL SURFACE 4.2 CELL ENVIRONMENT 4.3 CELL RECOGNIZATION
4.4 CELL JUNCTION

3 An overview of cells interact with their environment

4 4.1 Cell Surface ◆在结构上，包括： ●细胞被(cell coat) ●细胞质膜
●表层胞质溶胶(corticol cytosol)

5 ◆在功能上： ●保护细胞,使细胞有一个相对稳定的内环境； ●参与细胞内外的物质交换和能量交换； ●参与信号的识别和信息的传递；
●参与细胞运动； ●维护细胞的各种形态； ●与免疫、癌变等有十分密切关系。

6 表层胞质溶胶(cytosol)： 其中含有高浓度的蛋白质,其厚度在哺乳类细胞为 μm,其中没有核糖体和线粒体, 但是有较多的微丝和微管,它们对于维持细胞的形态和运动具有重要作用。

7 细胞被 ◆Glycocalyx) ●组成： 由细胞表面的碳水化合物形成的质膜保护层，又称为多糖包被。 ●功能： The glycocalyx is thought to mediate cell-cell and cell-substratum interactions, provide mechanical protection to cells, and serve as a barrier to particles moving toward the plasma membrane.

8 电镜下的细胞表面

9 细胞表面结构

10 4.1.2 PLANT CELL WALLS 植物细胞壁的作用 ◆提供机械强度 ◆保护细胞免遭渗透及机械损伤
◆植物细胞壁是一个动态结构，能够进行很多活动: ●与细胞壁有关的酶能够吸收细胞外的营养，生成能够通过细胞膜进入细胞的小分子化合物。 ●细胞壁也可以作为物质通透的障碍，在代谢和分泌过程中起重要作用。

11 细胞壁的结构组成 ◆植物的细胞壁相当于动物细胞的细胞 外基质(!!!)： ●动物细胞的细胞外基质的主要成分是 蛋白质分子；
●植物的细胞壁主要是多糖，其中最主 要的是纤维素。 ◆植物细胞壁的骨架：纤维素

12 ◆植物细胞壁的骨架：纤维素 ●Cellulose molecules are organized into microfibrils that confer rigidity to the cell wall and provide resistance to tensile (pulling) forces. ? ●Each microfibril is 5-10 nm in diameter and is composed of bundles of 30 to 60 cellulose molecules oriented parallel to one another and held together by hydrogen bonds. ?

13 植物细胞壁中的纤维素 ？

14 ◆The matrix of the plant cell walls
■Hemicellulose ●Hemicelluloses are branched polysaccharides whose backbone consists of one sugar, such as glucose, and side chains of other sugars, such as xylose. ●Hemicellulose molecules bind to the surfaces of cellulose microfibrils, cross-linking them into a complex structural network.

15 ■Pectins： ●Pectins are a heterogeneous class of negatively charged polysaccharides containing galacturonic acid（半乳糖醛酸）； ●Like the glycosaminoglycans of animal cell matrices, pectins hold water and thus form an extensive hydrated gel（水合胶）that fills in the spaces between the fibrous elements； ●When a plant is attacked by pathogens, fragments of pectins released from the wall trigger a defensive response by the plant cell； ●Purified pectin is used commercially to provide the gel-like consistency of jams and jellies.

16 ■Structure Proteins: Structure Protein functions are not well understood. One class, the extensins, provide structural support and may form a barrier to invading microorganisms.

17 植物细胞壁的分泌合成 ◆中间层形成： 主要是果胶。果胶是相邻两细胞壁所共有，并且具有将两个细胞连接在一起的作用。 ◆初生壁形成：
是细胞正在生长时形成的。初生壁的厚度为 nm,与动物细胞的基膜相当。初生壁由纤维素、半纤维素、果胶和糖蛋白等松散组成。 ◆次生壁形成： 是在细胞停止生长后分泌形成的。主要是增加细胞壁的厚度和强度。次生壁主要在初生壁的内层。

18 PLANT CELL WALLS

19 4.2 Extracellular matrix ◆Many types of animal cells are surrounded by an extracellular matrix (ECM)--an organized network of extracellular materials that is present beyond the immediate vicinity of the plasma membrane. ◆The ECM is more than an inert packing material, it often plays a key regulatory role in determining the shape and activities of the cell . ◆能够分泌和形成细胞外基质的主要细胞类群是成纤维细胞(fibroblast)和其他特化组织的细胞。

20 For example: ●Enzymatic digestion of the ECM that surrounds cultured cartilage(软骨） cells or mammary gland epithelial cells causes a marked decrease in the synthetic and secretory activities of the cells. ●Addition of extracellular matrix materials back to the culture dish restores the differentiated state of the cells and their ability to produce their usual cell products.

21 Typical Extracellular matrix

22 ◆细胞外基质的组成可分为三大类∶ ●蛋白聚糖(proteoglycan) ●结构蛋白 如胶原和弹性蛋白，它们赋予基质一定的强度和韧性。
●黏着蛋白(adhesive proteins) 如纤连蛋白和层粘蛋白，它们促使细胞同基质结合。

23 4.2.1 细胞外基质的基础物质 蛋白聚糖(Proteoglycan,PG) ◆结构与功能
● Protein-polysaccharide complex is called a proteoglycan ●A proteoglycan consists of a core protein molecule to which chains of glycosaminoglycans (GAGs,糖胺聚糖) are covalently attached. ●Because of the negative charges borne on the sulfated GAGs, proteoglycans bind huge numbers of cations, which in turn bind large numbers of water molecules. As a result, proteoglycans form a porous, hydrated gel that fills the extracellular space like packing material and resists crushing (compression) forces.

24 Proteoglycan

25 ◆ Glycosaminoglycans ● Each glycosaminoglycan chain is composed of a repeating disaccharide; that is, it has the structure -A-B-A-B-A-, where A and B represent two different sugars. ● GAGs are highly acidic due to the presence of both sulfate and carboxyl groups attached to the sugar rings. ●糖胺聚糖的二糖单位之一是氨基己糖(氨基葡萄糖或氨基半乳糖), 故称为糖胺聚糖。 ●糖胺聚糖包括∶ 硫酸软骨素(chondroitin sulfate) 透明质酸(hyaluronic acid)等。

26 构成糖胺聚糖的二糖

27 ◆透明质酸(hyaluronic acid)
细胞外基质中发现的大多数糖胺聚糖 都是作为蛋白聚糖的一个成分而存在， 惟一例外的是透明质酸，它在细胞外 基质中也可游离存在。 透明质酸在结缔组织中起强化、弹性和润滑作用,具有抗压能力。

28 4.2.2 结构蛋白 胶原(Collagen) ◆基本特性：
●Collagen is a family of fibrous glycoproteins that are present only in extracellular matrices. ●Collagen is the single most abundant protein in the human body (constituting more than 25 percent of all protein), ● Collagens are found throughout the animal kingdom and are noted for their high tensile strength, that is, their resistance to pulling forces. It is estimated that a collagen fiber 1 mm in diameter is capable of suspending a weight of 10 kg without breaking. ● Collagen is produced primarily by fibroblasts, the cells found in various types of connective tissues, and also by smooth muscle cells and epithelial cells.

29 ◆胶原的类型 ●Nineteen distinct types of collagen have been identified.
●Each collagen type is restricted to particular locations within the body, but two or more different types are often present together in the same ECM.

30 ◆Structural features ●All collagen molecules are trimers consisting of three polypeptide chains, called  chains. ● Along at least part of their length, the three polypeptide chains of a collagen molecule are wound around each other to form a unique, rod-like triple helix

31 ●在胶原纤维内部,有分子内和分子间的交联。分子内交联是指原胶原的三条链之间的赖氨酸残基间的交联,分子间的交联是指不同原胶原间的赖氨酸交联。
这种分子间的交联,使得在胶原纤维内部形成胶原蛋白分子呈1/4平行交替排列,即一个原胶原的头部与下一个原胶原的尾部有一个小的间隙分隔。

32 Structural features

33 ◆胶原的组装

34 ◆胶原的合成、装配与运输 ●哺乳动物具有大约20种不同的胶原基因，编码各种不同组织所需要的胶原。
●首先是在粗面内质网上合成带有信号肽的前原胶原(preprocollagan)。 ●胶原纤维的加工组装始于内质网、在高尔基体中继续进行, 最后完成于细胞外。

35 胶原的合成、装配与运输

36 ◆胶原的作用 白，在这些组织的细胞外基质中,胶原 起着细胞外基质骨架作用; ◆胶原具有促进细胞生长的作用;
◆胶原是骨、腱和皮肤组织中的主要蛋 白，在这些组织的细胞外基质中,胶原 起着细胞外基质骨架作用; ◆胶原具有促进细胞生长的作用; ◆在细胞分化中，胶原基质和提纯的胶 原底物具有维持并诱导细胞分化的作 用。

37 胶原酶遗传缺陷 某些人具有胶原酶的遗传缺陷，这样,他们的胶原纤维就不能正确地装配，其结果，皮肤和各种其它的结绨组织就会降低它们的强度变得非常的松弛。

38 皮肤过渡松弛症

39 弹性蛋白(Elastin) ◆是弹性纤维(elastic fibers)的主要成分。 ◆功能：能够赋予细胞外基质弹性。 ◆弹性蛋白也是富含甘氨酸和脯氨酸的蛋白质。与同胶原不同的是，弹性蛋白的脯氨酸没有羟基化，所以没有羟脯氨酸的存在。

40 弹性蛋白的结构

41 4.2.3 黏着蛋白 黏着蛋白(adhesive protein)是细胞外基中质的第三类成分，之所以将这些蛋白称为黏着蛋白，主要是这些些蛋白起着将细胞外基质与细胞联系起来的桥梁作用。

42 纤粘连蛋白(Fibronectin,FN)
◆存在： ● Fibronectin are a family of closely related adhesive glycoproteins that widely distributed throughout the animal kingdom; ●Fibronectin occurs in a soluble form in the blood and other body fluids； ●As insoluble fibrils in the extracellular matrix 。

43 ◆结构特点： ■ Fibronectin polypeptide is constructed from a sequence of approximately 30 independently folding Fn domains ■ Each of the two polypeptide chains that make up a fibronectin molecule contains： ●Binding sites for other components of the ECM, such as collagens and proteoglycans. These binding sites facilitate interactions that link these diverse molecules into a stable, interconnected network. ●Binding sites for receptors on the cell surface，these binding sites hold the cell in a stable attachment to the ECM .

44 Fibronectin

45 ◆RGD序列 ●用蛋白酶消化纤粘连蛋白与细胞结合区, 发现这一结构域中Arg-Gly-Asp三肽序列负责同细胞表面的结合,
●Arg-Gly-Asp序列(又称RGD序列)同样存在于细胞外基质和血液的其它类型的黏着蛋白序列中。

46 ◆功能： ◆FN最主要的功能是介导细胞的黏着。
◆由于FN具有同时与细胞外基质各类成分相结合的特点,并可促进细胞外基质的其它成分的沉积,故认为FN是细胞外基质的组织者。

47 层粘连蛋白(laminin, LN) ◆Laminins are a family of extracellular glycoproteins that consist of three different polypeptide chains linked by disulfide bonds and organized into a molecule resembling a cross with three short arms and one long arm ？ ◆层粘连蛋白主要存在于基膜(basal lamina)结构中，是基膜的主要结构成分。

48 Laminin

49 ◆层粘连蛋白的功能 ■首先作为基膜的主要结构成分对基膜的组装起关键作用。它可作为黏着因子介导细胞黏着于胶原,使之发生铺展。 ■Extracellular laminins can greatly influence a cell's potential for migration, growth, and differentiation.

50 基膜(Basement membrane )
4.2.4 细胞外基质与细胞的相互作用 基膜(Basement membrane ) ◆Basement membrane (or basal lamina) is a continuous sheet 50 to 200 nm thick: ■ Surrounds muscle and fat cells; ■ Underlies the basal surface of epithelial tissues, such as the epidermis of the skin, or the lining of the digestive and respiratory tracts, ■ Underlies the inner endothelial lining of blood vessels.

51 ◆基膜的组成 ■层粘连蛋白 是基膜的主要成分，也是基膜的组织者； ■巢蛋白(entactin) ■Ⅳ型胶原 ■硫酸肝素糖蛋白。
Ⅳ型胶原是基膜的核心分子，排列成网状；层粘连蛋白同Ⅳ型胶原结合，覆盖在细胞表层。

52 基膜的结构组成

53 ◆基膜的功能 ●Basement membranes provide mechanical support for the attached cells; ●Serve as a substratum for cell migration; ●Separate adjacent tissues within an organ; ●Basement membranes also serve as a barrier to the invasion of tissues by errant cancer cells.

54 Matrix metalloproteinases (MMPs)
◆The degradation of ECM materials is accomplished largely by a family of zinc-containing enzymes called matrix metallopro-teinases that are either secreted into the extra-cellular space or bound to the external surface of the plasma membrane. ◆The excessive or inappropriate activity of MMPs is likely to cause disease. In fact, MMPs have been implicated in a number of pathological conditions, including arthritis, multiple sclerosis, atherosclerosis, tooth decay, and tumor progression .

55 整联蛋白(integrin) ◆Integrins are a family of integral membrane proteins thought to be present on the surfaces of virtually all types of vertebrate cells.

56 ◆整联蛋白结构: ●Integrins are composed of two membrane-spanning polypeptide chains, an  chain and a  chain, that are noncovalently linked. ●Two subunits are arranged so as to form a globular extracellular head connected to the membrane by a pair of rigid stalks . ● Both subunits have a single transmembrane helix and a small cytoplasmic domain. ● N-terminal extracellular portion of the subunit consisted of seven repeating modules, each comprised of approximately 60 amino acids. ●This portion of the polypeptide is folded into a single domain of a type that had been termed a seven-bladed  propeller. ●Three calcium ions are seen to be present as part of blades 5, 6, and 7.

57 整联蛋白

58 整联蛋白

59 ◆整联蛋白类别 ●At least 18 different  subunits and 8 different  subunits have been identified. ● Although more than a hundred possible pairings of  and subunits could theoretically occur, only about two dozen different integrins have been identified on the surfaces of cells ?

60 ◆整联蛋白的活性 Integrins have been implicated in two major types of activities: ■ Adhesion of cells to their substratum (or to other cells) ■ Transmission of signals from the external environment to the cell interior. ●The binding of the extracellular domain of an integrin to a ligand, such as fibronectin or laminin, can induce a conformational change at the cytoplasmic end of the integrin. ● Changes at the cytoplasmic end can, in turn, alter the way the integrin interacts with nearby cytoplasmic proteins, such as the enzyme focal adhesion kinase (FAK)

61 整联蛋白与细胞外受体相连

62 细胞与细胞外基质