Cell Adhesion and Extracellular Matrix

Cells in tissues can adhere directly to one another (cell–cell adhesion) through specialized integral membrane proteins called cell-adhesion molecules (CAMs) that often cluster into specialized cell junctions.

Cells in animal tissues also adhere indirectly (cell–matrix adhesion) through the binding of adhesion receptors in the plasma membrane to components of the surrounding extracellular matrix (ECM).

These two basic types of interactions not only allow cells to aggregate into distinct tissues but also provide a means for the bidirectional transfer of information between the exterior and the interior of cells.

CAMs can be broadly distributed along the regions of plasma membranes that contact other cells or clustered in discrete patches or spots called cell junctions. The extracellular matrix (ECM) is a complex meshwork of proteins and polysaccharides that contributes to the structure and function of a tissue.

Cell-adhesion molecules (CAMs) mediate direct cell–cell adhesions and cell-surface adhesion receptors mediate cell–matrix adhesions. These interactions bind cells into tissues and facilitate communication between cells and their environments. The cytosolic domains of CAMs and adhesion receptors bind multifunctional adapter proteins that mediate interaction with cytoskeletal fibers and intracellular signaling proteins.

The major families of cell-surface adhesion molecules are the cadherins, selectins, Ig- superfamily CAMs, and integrins.

Tight cell–cell adhesions entail both cis (lateral or intracellular) oligomerization of CAMs and trans (intercellular) interaction of like (homophilic) or different (heterophilic) CAMs.

Tight junction

Adherens junction

Desmosome

Gap junction

Certain cell-surface receptors, including some integrins, can bind components of the extracellular matrix (ECM), thereby indirectly adhering cells to each other through their interactions with the matrix. Three abundant ECM components are proteoglycans, a unique type of glycoprotein; collagens, proteins that often form fibers; and soluble multiadhesive matrix proteins (e.g., fibronectin).

ECM

Collagen

proteoglycans

Fibronectin

The relative volumes of cells versus matrix vary greatly among different animal tissues and organs. Some connective tissue, for instance, is mostly matrix, whereas many organs are composed of very densely packed cells with relatively little matrix.

Although the extracellular matrix generally provides mechanical support to tissues, it serves several other functions as well. Different combinations of ECM components tailor the extracellular matrix for specific purposes: strength in a tendon, tooth, or bone; cushioning in cartilage; and adhesion in most tissues.

In addition, the composition of the matrix, which can vary, depending on the anatomical site and physiological status of a tissue, can let a cell know where it is and what it should do (environmental cues).

The matrix also serves as a reservoir for many extracellular signaling molecules that control cell growth and differentiation. In addition, the matrix provides a lattice through or on which cells can move, particularly in the early stages of tissue assembly.

Morphogenesis—the later stage of embryonic development in which tissues, organs, and body parts are formed by cell movements and rearrangements—also is critically dependent on cell–matrix adhesion as well as cell–cell adhesion.