Chapter  22:  Integrating Cells into Tissues

A dense network of elastin and collagen fibers form the extracellular matrix of elastic cartilage. These fibers of the ECM are intimately connected to the plasma membrane of a chondrocyte. The membrane is supported by the network of filaments from the actin cytoskeleton. [Courtesy of R. Mecham and J. Heuser, Washington University School of Medicine.]

The evolution of multicellular organisms permitted specialized cells and tissues to form; a flowering plant has at least 15 cell types, and a vertebrate hundreds. In both plants and animals, cells that are specialized to carry out a particular task are found together in the tissues in which the task is performed: a xylem or meristem; a liver, a muscle, or a nerve ganglion. Different types of cells in a tissue are often arranged in precise patterns of staggering complexity. For instance, the hundreds of different types of neurons in the human brain are interconnected to one another through a network of some 10¹⁵ synaptic connections! The coordinated functioning of many types of cells within tissues, and of multiple specialized tissues, permits the organism as a whole to move, metabolize, reproduce, and carry out other essential activities.

A key step in the evolution of multicellularity must have been the ability of cells to contact tightly and interact specifically with other cells. Various integral membrane proteins, collectively termed cell-adhesion molecules (CAMs), enable many animal cells to adhere tightly and specifically with cells of the same, or similar, type; these interactions allow populations of cells to segregate into distinct tissues (Figure 22-1). Following aggregation, cells elaborate specialized cell junctions that stabilize these interactions and promote local communication between adjacent cells. Animal cells also secrete a complex network of proteins and carbohydrates, the extracellular matrix (ECM), that creates a special environment in the spaces between cells. The matrix helps bind the cells in tissues together and is a reservoir for many hormones controlling cell growth and differentiation. The matrix also provides a lattice through which cells can move, particularly during the early stages of differentiation. Defects in these connections lead to cancer and developmental malformations.

The extracellular matrix has three major protein components: highly viscous proteoglycans, which cushion cells; insoluble collagen fibers, which provide strength and resilience; and soluble multiadhesive matrix proteins, which bind these components to receptors on the cell surface. Different combinations of these components tailor the strength of the extracellular matrix for different purposes. For example, animals contain many types of extracellular matrices, each specialized for a particular function such as strength (in a tendon), cushioning (in cartilage), or adhesion. In the case of smooth muscle cells that surround an artery, the extracellular matrix must provide strong but flexible connections.

The extracellular matrix is not just an inert framework or cage that supports or surrounds cells. The matrix also communicates directly and indirectly with the intracellular signaling pathways that direct a cell to carry out specific functions. For example, the ability of hepatocytes—the principal cells in the liver—to express liver-specific proteins depends on their association with a matrix of appropriate composition. Specific ECM components can directly activate cytosolic signal-transduction pathways by binding to cell-adhesion protein receptors in the plasma membrane. Alternatively, by binding growth factors and other hormones, the matrix can either sequester these signals from cells or, conversely, present them to cells, thereby indirectly inducing or inhibiting signaling pathways. Morphogenesis—the later stage of embryonic development during which form is achieved by cell movements and rearrangements—also is critically dependent on ECM components, which are constantly being remodeled, degraded, and resynthesized locally. Even in adults—in areas of wounding, for example —degradation and resynthesis of ECM components occurs. How the extracellular matrix regulates cell activities is considered in other chapters on signaling and development.

In this chapter, we focus on the structure of and interactions between ECM components, cell-adhesion molecules, and cell-adhesion junctions—the main structures that permit animal cells to form organized tissues. Plant cells are surrounded by a cell wall that is thicker and more rigid than the extracellular matrix. Although the plant cell wall and the extracellular matrix serve many of the same functions, they are structurally very different. Because of these differences, we discuss the plant cell wall and its interactions with plant cells in a separate section at the end of the chapter.