Extracellular Matrix

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.

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 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) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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.

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

Structure and Function of the Extracellular Matrix: A Multiscale Quantitative Approach introduces biomechanics and biophysics with applications to understand the biological function of the extracellular matrix in health and disease. A general multiscale approach is followed by investigating behavior from the scale of single molecules, through fibrils and fibers, to tissues of various organ systems. Through mathematical models and structural information, quantitative description of the extracellular matrix function is derived with tissue specific details. The book introduces the properties and organization of extracellular matrix components and quantitative models of the matrix, and guides the reader through predicting functional properties. This book integrates evolutionary biology with multiscale structure to quantitatively understand the function of the extracellular matrix. This approach allows a fresh look into normal functioning as well as the pathological alterations of the extracellular matrix. Professor Suki's book is written to be useful to undergraduates, graduate students, and researchers interested in the quantitative aspects of the extracellular matrix. Researchers working in mechanotransduction, respiratory and cardiovascular mechanics, and multiscale biomechanics of tendon, cartilage, skin, and bone may also be interested in this book. Examines the evolutionary origins and consequences of the extracellular matrix Delivers the first book to quantitatively treat the extracellular matrix as a multiscale system Presents problems and a set of computational laboratory projects in various chapters to aid teaching and learning Provides an introduction to the properties and organization of the extracellular matrix components