Introduction and Goals
This tutorial describes some aspects of how cells are organized in multicellular organisms. You will learn about the mechanisms by which cells adhere to an extracellular network and to each other, and how they become organized into functional units. You will explore the molecules that mediate this organization and that confer the distinct properties of structure and function. Plant cells have a unique feature that contributes to their overall morphology, and this will be described. Finally, you will learn about the properties of stem cells, a unique cell type that has promoted exciting and currently, controversial research.
By the end of this tutorial you should know:
- The function and properties of connective tissue
- The composition of connective tissue, including structural proteins, adhesive glycoproteins, proteoglycans and glycosaminoglycans
- The unique properties and composition of the plant extracellular matrix
- The polarized nature of epithelial cells
- The cell junctions of epithelial cells, including tight junctions, gap junctions and adhesive junctions
- The several different types of cell adhesion molecules
- The properties of stem cells
Animals Have Four Primary Tissues
Cells with similar properties can be categorized as part of the same tissue. Organsare formed by the interaction of one or more tissues that form a structural and functional unit (e.g. the heart). There are four primary tissues in animals: connective, epithelial, muscle and nervous. In this tutorial, some of the unique cellular and molecular properties of connective and epithelial tissues will be described. Connective tissueis distinct from the other primary tissues because it consists of cells that are surrounded by a large amount of extracellular material. Epithelial tissueconsists of cells that form membranes that cover and line the body surface and cavities, and cells that form glands that secrete hormones and other substances. Muscle tissue consists of cells specialized for contraction. Nervous tissue consists of neurons, cells specialized for the conductance and transmission of electrochemical impulses, as well as support cells (review Tutorial on Membrane Potential, Ion Transport and Nerve Impulse).
Functions of Connective Tissue
Composition of the animal ECM
Collagen, a structural protein of the ECM
The most abundant protein found in animals is collagen. It is the predominant structural component of the ECM of bones, cartilage, tendons and skin. In vertebrates there are many different types of collagens, encoded for by over 20 different genes. Collagen types in the ECM are tissue specific. However, there are two distinguishing features of all collagens: their unusual amino acid composition and their organization into rigid fibers. Collagens consist of large amounts of the amino acids glycine and proline, as well as two unusual amino acids, hydroxylysine and hydroxyproline. All collagens in the ECM are thick, rigid fibers composed of many molecules of collagen packed together by hydrogen bonding. In fibroblasts, three collagen polypeptides are wound together in a triple helix, referred to as procollagen, and then secreted. The presence of glycine at every third residue in the collagen polypeptides facilitates the formation of this triple helix because of all the amino acids, glycine has the smallest side chain; thus, glycine allows the collagen polypeptides to be held together tightly. Outside the cell, the ends of procollagen are cleaved to allow it to assemble into a collagen fibril, which, in turn, assembles into collagen fibers. The organization of collagen fibers is tissue specific and is regulated by the fibroblasts that secrete the collagen polypeptides. For example, in skin the collagen fibers are crisscrossed so that tension is provided in any direction, whereas in tendons the collagen fibers lie parallel to each other, between the muscle and bone, to provide strength in one axis.
Adhesive Glycoproteins of the ECM
Adhesive glycoproteins, both in the ECM and on cell surfaces, allow the adhesion of cells to the ECM (see Figure 1). Fibronectinis one of the most common adhesive glycoproteins. It is a modular protein that has binding sites for collagen, as well as other components of the ECM, and binding sites for the cell surface; thus, fibronectin provides a link between the ECM and the cells that adhere to it. There are two major types of fibronectins, both encoded for by the same gene: tissue fibronectin is found in the ECM of connective tissue, and soluble plasma fibronectin is found in blood, where it promotes blood clotting. Laminin, another adhesive glycoprotein found in the specialized ECM, is associated with epithelial cells (Figure 1).
Integrins are located on the surfaces of many of the cells that grow and adhere to the ECM. This class of transmembrane receptor proteins can bind fibronectin and laminin in the ECM (Figure 1). In addition, integrins can bind cell surface proteins. The extracellular domain of an integrin receptor binds to adhesive glycoproteins in the ECM, whereas the intracellular domain binds to the cytoskeleton, thereby ensuring that the cell is securely anchored to the ECM. Furthermore, integrins play roles in cell signaling and can trigger intracellular signal transduction cascades, thereby linking adhesion to the ECM with changes in the growth and fate of a cell.
Proteoglycans and GAGs in the ECM
The plant cell wall
Plant cells are surrounded by a tough cell wall, which is the predominant ECM in plants. The cell wall provides strength in plant tissues. The primary component of the plant cell wall is the polysaccharide cellulose. Cellulose is synthesized extracellularly by enzyme complexes embedded in the plasma membrane of the cell, and is deposited in oriented rigid fibers. Initially, a cell will synthesize a thin primary cell wall that is capable of expanding as the cell grows. Once the tissue has stopped growing, a more rigid secondary cell wall is deposited. In addition to cellulose, there are other polysaccharides and some structural glycoproteins that interact to form a strong and solid ECM. In the case of woody tissue there is another type of molecule in the ECM, lignin, which forms a large crosslinked network that is very strong and can support the weight of a large tree.
Epithelial Cells: Polarized Cells
Epithelial tissue is widespread and varied, however, all cells of epithelial tissues organize into multicellular sheets that line or cover many surfaces and cavities. This cellular organization is achieved through a variety of mechanisms that allow cell adhesion and coordination. Cells within an epithelial sheet are polarized with two distinct sides: the apical surface, which is exposed to air or fluid; and the basal surface, which is attached to a distinct thin layer of ECM referred to as the basal lamina. The attachment of the epithelial sheet to the basal lamina is mediated by a distinct junction called the hemidesmosome. The extracellular domain of integrin on the epithelial cells recognizes and binds the adhesive glycoprotein laminin in the ECM. The intracellular domain of integrin is anchored to the cytoskeleton by binding to intermediate filaments.
The two surfaces of the epithelial cells have very different properties and functions. Consider the epithelial cells lining the small intestine. The apical surface faces the lumen of the small intestine, and is primarily responsible for absorption of nutrients. The basal surface adheres to the underlying basal lamina, and is primarily responsible for exporting nutrients into the bloodstream. The apical and basal membranes have distinct protein compositions that mediate these different activities; the apical surface contains sodium/glucose symporters to import glucose against its concentration gradient, whereas the basolateral surface contains glucose transporters to export glucose down its concentration gradient (see Tutorial on Passive and Active Transport).
Figure 3. Cell junctions in epithelial cells. Epithelial cells are polarized, having apical and basolateral membrane domains. The tight junction is a unique feature of epithelial cells. It seals the extracellular space between two adjacent cells. It also restricts the lateral movement of proteins in the membrane, maintaining the asymmetric distribution of apical and basolateral membrane proteins. Gap junctions, which are common in epithelial cells, are channels that connect two adjacent cells and allow the passage of small solutes and ions. In epithelial cells, there are two types of adhesive junctions: the adherens junction (a band of adhesion, between two cells, that is located more apically) and the desmosome (a distinct spot of adhesion). These differ in their intracellular attachment to the cytoskeleton. Adherens junctions are linked to actin filaments, whereas desmosomes are linked to intermediate filaments. In addition, epithelial cells adhere to the basal lamina via hemidesmosomes.
Cells in an epithelium function as a single continuous sheet of cells, closely juxtaposed, firmly attached and coordinately regulated. Epithelial cells have a variety of cell junctions that allow this type of tissue organization (illustrated in Figure 3). There is a distinct junction right below the apical surface of epithelial cells, termed thetight junction, which seals the gap between two epithelial cells in a sheet. The plasma membranes of adjacent cells are closely juxtaposed through the binding of transmembrane proteins on adjacent cells, which fills the extracellular space and serves to prevent the diffusion of solutes into the space between adjacent cells. This allows the tissue to act as an effective barrier; diffusion between cells is restricted, so only regulated transport through the cells can occur. Furthermore, the tight junction serves to maintain the polarity of epithelial cells because it inhibits the lateral movement of membrane proteins, thereby restricting proteins to either the apical or basolateral domains.
A gap junction is a second type of cell junction in epithelial cells as well as other tissues (including muscle). The gap junction is a channel between two adjacent cells that allows the diffusion of small hydrophilic solutes and ions between the two cells. Gap junctions are composed of transmembrane proteins called connexins. Six subunits of connexin form a cylindrical channel through the plasma membrane of one cell, and are linked to a similar channel in the adjacent cell. Gap junctions allow diffusion of ions, second messengers involved in signaling pathways (e.g. cAMP), and metabolites (e.g. ATP) between cells. This allows electrochemical continuity, rapid communication and uniform activity in cells organized into a tissue.
An adhesive junction is a third type of cell junction in epithelial cells. It allows cells to bind tightly to their neighbors and to be integrated into a tissue. Characteristically, the adhesive junction is mediated by the extracellular binding of a class of transmembrane proteins called cadherins. Cadherin molecules mediate cell recognition because the extracellular domains bind to the same cadherin on an adjacent cell (see Figure 4). They anchor the two cells together because the intracellular domain binds to the cytoskeleton. There are two distinct types of adhesive junctions: the adherens junction and the desmosome. In epithelial cells the adherens junction is a band encircling the apical surface of the cell. In other cell types it is a small point of attachment. Cadherins that participate in this type of junction are linked to actin in the cytoskeleton via their intracellular domains. The desmosomeis a small disc of adhesion between two cells. It is mediated by a distinct type of cadherin that is linked to the intermediate filaments in the cytoskeleton. The hemidesmosome, described earlier, is similar to the desmosome, however, it anchors the cell to the basal lamina as opposed to another cell.
Plant cells do not have any of these types of cell junctions. Instead, they are separated by cell walls. They do, however, have a structure (plasmodesma) analogous to the gap junction, which allows the movement of small molecules and ions between adjacent cells. The plasmodesmata are channels through the cell walls, composed of plasma membranes, which connect two adjacent plant cells.
Cell Recognition and Adhesion
Tissue Renewal and Stem Cells
This tutorial defined connective tissue and epithelial tissue, and addressed their unique cellular and molecular properties. Connective tissue is surrounded by large amounts of extracellular material, and can be flexible or rigid. The extracellular matrix (ECM) of animals is mostly collagen. Cells adhere to the ECM via adhesive glycoproteins (e.g., fibronectin and laminin). Integrins are transmembrane receptor proteins that further ensure cell anchoring, as well as play a role in cell signaling. Proteoglycans and glycosaminoglycans (GAGs) confer the ECM with the ability to resist compression. The ECM of plants is predominantly the cell wall, composed primarily of cellulose. Lignin is also part of the plant ECM.
Epithelial tissue forms membranes that cover and line body surfaces and cavities, and forms glands. Epithelial sheets have an apical and basal surface, both of which have different properties and functions. Cell junctions allow tissue organization in the epithelium. These include: tight junctions, which separate epithelial cells within a sheet; gap junctions, which via a channel, allow diffusion of certain solutes and ions between cells within a sheet; and adhesive junctions, which allow the tight bonding of cells and their integration into tissues. None of these cell junctions are found in plants. Plant cells are separated by cell walls that contain plasmodesma (functionally analogous to the gap junction).
Three types of adhesion proteins were discussed: cell adhesion molecules (CAMs), cadherins, and integrins. These transmembrane proteins function in cell recognition and adhesion during tissue formation.
Finally, stem cells were discussed. Stem cells can self-renew and give rise to differentiated cells; that is, the new differentiated cells "stem" from the precursor stem cell population. Adult stem cells are generally limited to one type of tissue, with usually a narrow range of cell types. Conversely, embryonic stem cells can potentially give rise to a greater diversity of cell types, and hence, might be a source for every differentiated cell type.