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

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.

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.

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

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.

This new volume in the Subcellular Biochemistry series will focus on the biochemistry and cellular biology of aging processes in human cells. The chapters will be written by experts in their respective fields and will focus on a number of the current key areas of research in subcellular aging research. Main topics for discussion are mitochondrial aging, protein homeostasis and aging and the genetic processes that are involved in aging. There will also be chapters that are dedicated to the study of the roles of a variety of vitamins and minerals on aging and a number of other external factors (microbiological, ROS, inflammation, nutrition). This book will provide the reader with a state of the art overview of the subcellular aging field. This book will be published in cooperation with a second volume that will discuss the translation of the cell biology of aging to a more clinical setting and it is hoped that the combination of these two volumes will bring a deeper understanding of the links between the cell and the body during aging.

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.

Knowledge about the mechanisms of lung development has been growing rapidly, especially with regard to cellular and molecular aspects of growth and differentiation. This authoritative international volume reviews key aspects of lung development in health and disease by providing a comprehensive review of the complex series of cellular and molecular interactions required for lung development. It covers such topics as pulmonary hypoplasia, effects of malnutrition, and pulmaonary angiogenesis. An indispensable reference for all those involved in studying or treating lung disease in neonates and children, the book offers a unique view of the development of this essential organ.

This book covers different omics aspects related to the extracellular matrix (ECM), namely specific omics resources focused on the extracellular matrix (e.g., databases, repositories and atlases), quantitative proteomics applied to specific extracellular matrices (e.g. basement membranes), biological processes such as ECM degradation (degradomics), cell-matrix interactions (adhesomes), signaling pathways, biomarker discovery and diseases, and interactomics (extracellular matrix interaction networks including not only protein-protein but also protein-glycosaminoglycan interactions). The volume also includes recent advances in glycomics and glycobioinformatics applied to proteoglycans and glycosaminoglycans, which are key biological players. The use of omics data to build dynamic models of ECM-regulated biological pathways is addressed, together with the requirement to standardize omic data, which is a prerequisite for the FAIR (Findability, Accessibility, Interoperability, and Reusability) guiding principles for scientific data management. This book will be of great interest to a broad readership from beginners to advanced researchers, who are interested in extracellular matrix omics and will inspire future research topics.

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