Extracellular Matrix

The tissues of a multicellular organism contain two main components, the cells themselves, onwhichmost biological research has traditionally focused, and the material that lies between the cells. This material is called the extracellular matrix, usually abbreviated to ‘ECM’. The ratio of tissue volume occupied by ECM to that occupied by cells varies from less than 1:10 (e.g. in muscles) to more than 10:1 (e.g. in tendons, cartilage and bone). For many years, ECMwas dismissed as a relatively inert ‘ground substance’ whose sole function was packing. However, it has now become clear that the ECM is much more complex than was once supposed and that interactionwith the surrounding matrix is one of the major controls of cell behaviour. The main functions of ECM are to fill space between cells, to provide a barrier that isolates tissues from each other, to provide navigational cues for migratory cells, to provide signals that alter cell behaviour, and to sequester biologically active compounds such as growth factors. ECM of one sort or another is a feature of all multicellular organisms. In plants, ECM appears mainly as cell walls, while in animal tissues it appears in two main forms: basementmembranes and stromal matrix (Figure 1). Basement membranes are thin layers of ECM gel that underlie epithelial cell sheets, the basement membrane effectively separating the epithelium from underlying connective tissues. Stromal matrix is associated with ‘connective tissues’ and is frequently fibrous, particularly in load-bearing tissues such as artery walls, tendons, cartilage and skin. Some stromal ECM is also mineralized, to produce bone. The ECM is a mixture of many different molecular components that varies between organisms and also between tissues within one organism, and sometimes also varies with developmental age. The internal structure of the ECM is highly organized, the organization arising partly from the innate properties of its constituent molecules and partly from the activities of the cells that produce it. Cells embedded in the ECMmake contact with it mainly through specialized matrix receptor molecules. These allow the cells to adhere to the matrix and may also signal the presence of particular matrix components to the internal machinery of the cell, allowing the matrix to control cell behaviour. The ECM is not a static structure, but is constantly being remodelled by the cells within and around it and by the opposing influences of ECMsynthesis and its destruction by proteolytic enzymes. This article will describe the main components of the ECM in plant and animal tissues, how they are synthesized and organized, and how ECM receptors work. Then it will give an overview of how the ECM is used by cells to allow them to move, to make complex tissue shapes and to differentiate into different types of specialized cells. Finally, it will briefly review the diseases that arise when the formation and maintenance of the ECM and ECM receptors goes awry.