Current concepts of extracellular matrix

General principles of ECM organization are well known. Organized fibrous polymers, including collagens, elastins, and resilins, are embedded within an amorphous mixture of nonfibrous components as the fundamental theme. The need for inextensibility coupled with great strength mandates the presence of fibrous macromolecules, primarily those that aggregate into near crystalline arrays such as the collagens.6 Tissue resilience becomes predominant when elastic fibers such as elastin and resilin are strategically located in tissues. The amorphous substances in the ECM are predominantly proteoglycans, which can impart turgor.7,8 Adhesive glycoproteins, such as laminin, fibronectin, and entactin (nidogen), are enriched in basement membranes9–13 and are specifically recognized by discrete integrins. The relative proportion of fibrous and nonfibrous components partially dictate the overall physical properties of a particular ECM, as does the diameter and weave of the fibers and the organizational arrangement of nonfibrous substances. We recognize ECM proteins as large, multifunctional molecules. They contain many domains, often repeated and occurring in tandem with each other. The domains yield various threedimensional structures, often imparting several functions to one macromolecule.2 Such functions include recognition by integrins and other cell receptors, ability to form coiled coils, predisposition to oligomerize, specific recognition by metalloproteinases,14,15 and ability to form distinct intramatrix interactions. I dedicate this lecture to the memory of Professor Katsuyuki Fujii, MD. Early in his career Professor Fujii studied as a postdoctoral research fellow in my laboratory. He was one of my most outstanding students and has been acclaimed as a leader by the international orthopedic community.