In the ten-year interval since the first edition of this volume went to press, our knowledge of extracellular matrix (ECM) function and structure has enor mously increased. Extracellular matrix and cell-matrix interaction are now routine topics in the meetings and annual reviews sponsored by cell biology societies. Research in molecular biology has so advanced the number of known matrix molecules and the topic of gene structure and regulation that we won dered how best to incorporate the new material. For example, we deliberated over the inclusion of chapters on molecular genetics. We decided that with judicious editing we could present the recent findings in molecular biology within the same cell biology framework that was used for the first edition, using three broad headings: what is extracellular matrix, how is it made, and what does it do for cells? Maintaining control over the review of literature on the subject of ECM was not always an easy task, but we felt it was essential to production of a highly readable volume, one compact enough to serve the the student as an introduction and the investigator as a quick update on graduate the important recent discoveries. The first edition of this volume enjoyed con hope the reader finds this edition equally useful. siderable success; we D. Hay Elizabeth vii Contents Introductory Remarks 1 Elizabeth D. Hay PART I. WHAT IS EXTRACELLULAR MATRIX? Chapter 1 Collagen T. F. Linsenmayer 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 2. The Collagen Molecule . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 2. 1. Triple-Helical Domain(s) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Knowledge of the extracellular matrix (ECM) is essential to understand cellular differentiation, tissue development, and tissue remodeling. This volume of the series “Biology of Extracellular Matrix” provides a timely overview of the structure, regulation, and function of the major macromolecules that make up the extracellular matrix. It covers topics such as collagen types and assembly of collagen-containing suprastructures, basement membrane, fibronectin and other cell-adhesive glycoproteins, proteoglycans, microfibrils, elastin, fibulins and matricellular proteins, such as thrombospondin. It also explores the concept that ECM components together with their cell surface receptors can be viewed as intricate nano-devices that allow cells to physically organize their 3-D-environment. Further, the role of the ECM in human disease and pathogenesis is discussed as well as the use of model organisms in elucidating ECM function.

The complex and critical process of extracellular matrix (ECM) assembly is described in this book. Assembly may involve molecules interacting with molecules of the same matrix class, such as in collagen, or interactions between different ECM molecules, such as in basement membranes. The text shows how this is driven by structural information within the matrix monomer. This information will be of interest to cell, developmental, and molecular biologists, biochemists, biophysicists, and biomedical researchers involved in macromolecular assembly, biological macromolecules, and extracellular matrix. - Addresses assembly of most of the known classes of extracellular matrix macromolecules - Discusses higher order structures produced by ECM - Gives important concepts in ECM and cell-matrix interactions, Protein structure and protein-protein interactions, Development and tissue remodeling

Regulated turnover of extracellular matrix (ECM) is an important component of tissue homeostasis. In recent years, the enzymes that participate in, and control ECM turnover have been the focus of research that touches on development, tissue remodeling, inflammation and disease. This volume in the Biology of Extracellular Matrix series provides a review of the known classes of proteases that degrade ECM both outside and inside the cell. The specific EMC proteases that are discussed include cathepsins, bacterial collagenases, matrix metalloproteinases, meprins, serine proteases, and elastases. The volume also discusses the domains responsible for specific biochemical characteristics of the proteases and the physical interactions that occur when the protease interacts with substrate. The topics covered in this volume provide an important context for understanding the role that matrix-degrading proteases play in normal tissue remodeling and in diseases such as cancer and lung disease.

In most tissues, cells are surrounded by an extracellular matrix (ECM) containing proteins such as collagen, laminin, and fibronectin. The ECM plays an important role in regulating cell function. ECM proteins bind to integrins and other cell surface receptors, activating signaling pathways that regulate cellular morphology, adhesion, cell migration, cell proliferation, and apoptosis. Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Biology covers all aspects of ECM composition and function, as well as alterations in the ECM that occur during development, tumorigenesis, and other disease states. The contributors examine the various ECM proteins and proteoglycans, ECM receptors such as integrins, and the signaling pathways that mediate the effects of the ECM on cells. They also describe ECM functions in specific biological contexts, including angiogenesis, hemostasis, and thrombosis. Covering not only the biochemistry and cell biology of the ECM but also its roles in development, physiology, and pathology, this volume is an indispensable reference for cell biologists and all those interested in exploring the myriad functions of the ECM.

The evolution of single cells into multicellular organisms was mediated, in large part, by the extracellular matrix. The proteins and glycoconjugates that make up the extracellular matrix provide structural support to cellular complexes, facilitate cell adhesion and migration, and impart mechanical properties that are important for tissue function. Each class of ECM macromolecule has evolved to incorporate distinctive properties that are defined by conserved modules that are mixed together to achieve appropriate function. This volume provides a comprehensive analysis of how the major ECM components evolved over time in order to fill their specific roles found in modern organisms. The major focus is on the structural matrix proteins, matricellular proteins, and more complex ECM structures such as basement membranes. Adhesive proteins and their receptors are also discussed.

Cancer was thought to originate from alterations in intercellular signaling that resulted in the transformation of cells, their uncontrolled proliferation and metastasis. There is now an increasing body of evidence demonstrating that the surrounding matrix and cell-matrix interactions are also major players in this process. Cells adhere and receive signals from various extracellular matrices via transmembrane receptors, the best known of which are the heterodimeric glycoproteins, integrins.

In the last several years, the development of reagents that recognize smooth muscle-specific proteins has enabled researchers to identify smooth muscle cells (SMC) in tissue undergoing both differentiation and repair. These developments have led to increased research on SMC. The latest volume in the Biology of the Extracellular Matrix Series takes a current and all-encompassing look at this growing area of research. Devoted entirely to the subject of SMC, the book covers a diversity of topics-from SMC architecture and contractility to differentiation and gene expression in development. It also examines the proliferation and replication of SMC and its role in pharmacology and vascular disease. A must for cell, developmental, and molecular biologists, this book also will appeal to cardiologists, pathologists, and biomedical researchers interested in smooth muscle cells. - Presents a molecular, genetic, and developmental perspective of the vas smooth muscle cell - Overview sections highlight key points of chapters, including the clinical relevance of the research and expectations for future study - Appeals to both the basic biologist and to the biomedical researcher of vascular disease

This book aims at providing insights into the collagen superfamily and the remarkable diversity of collagen function within the extracellular matrix. Additionally, the mechanisms underlying collagen-related diseases such as dystrophic epidermolysis bullosa, osteogenesis imperfecta, as well as collagen-related myopathies and neurological disorders are discussed. Collagens are the most abundant extracellular matrix proteins in organisms. Their primary function is to provide structural support and strength to cells and to maintain biomechanical integrity of tissues. However, collagens can no longer be considered just as structural proteins. They can act as extracellular modulators of signaling events and serve critical regulatory roles in various cell functions during embryonic development and adult homeostasis. Furthermore, collagens are associated with a broad spectrum of heritability-related diseases known as “collagenopathies” that affect a multitude of organs and tissues including sensorial organs. The book is a useful introduction to the field for junior scientists, interested in extracellular matrix research. It is also an interesting read for advanced scientists and clinicians working on collagens and collagenopathies, giving them a broader view of the field beyond their area of specialization.