CHAPTER 4 Interactions Between Cells and Their Environment

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

An overview of cells interact with their environment

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)

◆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。

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0.1-0.2μm,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。

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.

电镜下的细胞表面

细胞表面结构

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。

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

◆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. ?

植物细胞壁中的纤维素 ？

◆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.

■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.

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

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100-200nm,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。

PLANT CELL WALLS

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。

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.

Typical Extracellular matrix

◆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。

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.

Proteoglycan

◆ 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。

构成糖胺聚糖的二糖

◆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。

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.

◆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.

◆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

●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。

Structural features

◆胶原的组装

◆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。

胶原的合成、装配与运输

◆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。

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。

皮肤过渡松弛症

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。

弹性蛋白的结构

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。

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 。

◆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 .

Fibronectin

◆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。

◆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。

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。

Laminin

◆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.

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.

◆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。

基膜的结构组成

◆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.

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 .

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.

◆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.

整联蛋白

整联蛋白

◆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. ?

◆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)

整联蛋白与细胞外受体相连

细胞与细胞外基质