History of extracellular matrix: a personal view.

Before the early 1800s, the "fibers" of connective tissue were thought to be the basis of life, which arose by spontaneous generation. With the discovery of cells in connective tissue, the cellular theory became accepted as the basis of life in about 1850. Material outside cells, but presumably made by cells, was recognized as the extracellular matrix. In the period from 1930 to 1975, the components of extracellular matrix were characterized by physical chemical, chemical and cell biological methods. For the major collagen of skin, tendon and bone, the molecular and fibril structures were determined; the aldehydederived crosslinks were discovered; its polypeptide chains were sequenced; and its biosynthesis and degradation were defined. This collagen, now type I collagen, was shown to be one of many types. The events of this period are described from the author's perspective. Since 1975, molecular and cell biological techniques have shown that the extracellular matrix is not the passive residence of cells but is highly interactive and plays a major role in health and disease.