In animals, the extracellular matrix (ECM) has multiple functions (see Table 20-2). The ECM helps organize cells into tissues and coordinates their cellular functions by activating intracellular signaling pathways that control cell growth, proliferation, and gene expression. The ECM can directly influence cell and tissue structure and function. In addition, it can serve as a repository for inactive or inaccessible signaling molecules (e.g., growth factors) that are released to function when the ECM is disassembled or remodeled by hydrolyases, such as proteases. Indeed, hydrolyzed fragments of ECM macromolecules can themselves have independent biological activity. The ensemble of proteins that compose the ECM itself and associated proteins that covalently modify (e.g., chemically cross-link, phosphorylate, cleave), bind to, or otherwise regulate the composition and structure of the ECM is called the matrisome. Proteomic (Chapter 3) and genomic analyses suggest that there are approximately 1030 and 1110 genes that encode the human and mouse matrisomes, respectively. Dysfunction of matrisome components can cause a wide variety of diseases that affect many different tissues and organs. It is noteworthy that there are ECM components, as well as extracellular domains of plasma-membrane proteins, that are phosphorylated on serine, threonine, or tyrosine side chains. Kinases that are present in the luminal compartments of the secretory pathway and some that are apparently secreted into the extracellular space catalyze these phosphorylations.

Many functions of the ECM and, indeed, some features of the assembly of the ECM require transmembrane adhesion receptors, including the integrins, that bind directly to ECM components and that also interact, through adapter proteins, with the cytoskeleton. Adhesion receptors bind to three types of molecules abundant in the ECM of all tissues (see Table 20-1):

We begin our description of the structures and functions of these major ECM components in the context of the basal lamina: the specialized sheet of ECM that plays a particularly important role in determining the overall architecture and function of epithelial tissues. In the following section, we discuss the ECM molecules commonly found in nonepithelial tissues, including connective tissue.