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

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.

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

Cells in the developing embryo depend on signals from the extracellular environment to help guide their differentiation. An important mediator in this process is the extracellular matrix – secreted macromolecules that interact to form large protein networks outside the cell. During development, the extracellular matrix serves to separate adjacent cell groups, participates in establishing morphogenic gradients, and, through its ability to interact directly will cell-surface receptors, provides developmental clocks and positional information. This volume discusses how the extracellular matrix influences fundamental developmental processes and how model systems can be used to elucidate ECM function. The topics addressed range from how ECM influences early development as well as repair processes in the adult that recapitulate developmental pathways.

Over the last decades cell biology and biological chemistry have increasingly turned their attention to the space between cells and revealed an elaborate network of macromolecules essential for structural support, cell adhesion and signaling. This comprehensive handbook of the extracellular matrix will give an overview of the current state of knowledge of matrix components (structure and function), their role in heath and disease (matrix pathobiology) and new aspects related to pharmacological targeting. It will provide an introduction to the extracellular matrix and detailed sections and chapters on: Importance of extracellular matrix in health and disease Matrix proteoglycans (aggrecan, versican, perlecan, SLRPs, syndecans, glypicans, serglycin) Matrix proteinases (remodeling, would healing, regulatory roles in health and disease, metalloproteinases, cystein proteases, plasmin and plasminogen activator system) Glycobiology (hyaluronan and sulfated glycosaminoglycans in cancer, inflammation and metabolic control) Collagens (supramolecular assembly, proteins binding collagen, scaffolds, bacterial and mutated collagens, procollagen proteinases) Cell surface receptors (integrins, syndecans, mechanical strain and TGFb, CD44 and DDR). Biotechnological and pharmacological outlook (matrix regulation by growth factors, hyaluronidases, pathobiology, disease targeting, delivery systems, EMT and proteomics). "The book Extracellular Matrix: Pathobiology and Signaling provides a comprehensive and up to date collection of very relevant topics for understanding the various facets of extracellular matrix and its interactions with cells in normal tissue as well as in disease. It represents the current front-line and will serve as a reference for extracellular matrix and posttranslational modifications." Dick Heinegård, Department of Clinical Sciences Lund, Section Rheumatology, Lund University, Sweden

The partition of fluid between the vascular and interstitial compartments is regulated by forces (hydrostatic and oncotic) operating across the microvascular walls and the surface areas of permeable structures comprising the endothelial barrier to fluid and solute exchange, as well as within the extracellular matrix and lymphatics. In addition to its role in the regulation of vascular volume, transcapillary fluid filtration also allows for continuous turnover of water bathing tissue cells, providing the medium for diffusional flux of oxygen and nutrients required for cellular metabolism and removal of metabolic byproducts. Transendothelial volume flow has also been shown to influence vascular smooth muscle tone in arterioles, hydraulic conductivity in capillaries, and neutrophil transmigration across postcapillary venules, while the flow of this filtrate through the interstitial spaces functions to modify the activities of parenchymal, resident tissue, and metastasizing tumor cells. Likewise, the flow of lymph, which is driven by capillary filtration, is important for the transport of immune and tumor cells, antigen delivery to lymph nodes, and for return of filtered fluid and extravasated proteins to the blood. Given this background, the aims of this treatise are to summarize our current understanding of the factors involved in the regulation of transcapillary fluid movement, how fluid movements across the endothelial barrier and through the interstitium and lymphatic vessels influence cell function and behavior, and the pathophysiology of edema formation. Table of Contents: Fluid Movement Across the Endothelial Barrier / The Interstitium / The Lymphatic Vasculature / Pathophysiology of Edema Formation