Biological Sciences
Extracellular Matrix
The extracellular matrix (ECM) is a complex network of proteins and carbohydrates that provides structural support and biochemical cues to cells in tissues and organs. It plays a crucial role in cell adhesion, migration, differentiation, and tissue development. The ECM also contributes to the regulation of cell signaling and tissue homeostasis.
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12 Key excerpts on "Extracellular Matrix"
- Abdul Aziz Nather, Glyn O Phillips(Authors)
- 2001(Publication Date)
- World Scientific(Publisher)
SECTION II: MATRIX BIOLOGY AND PHYSIOLOGY OF TISSUES This page is intentionally left blank Advances in Tissue Banking Vol. 5 © 2001 by World Scientific Publishing Co. Pte. Ltd. 6 THE ORGANISATION OF THE Extracellular Matrix GARETH J. THOMAS and MALCOLM DAVIES Institute of Nephrology University of Wales College of Medicine Heath Park, Cardiff CF14 4XN Wales, UK 1. Introduction The last decade has witnessed a rapid increase in our knowledge of the Extracellular Matrix (ECM) (Hay, 1999). This is largely due to advances in molecular biology that have greatly contributed to our understanding of the composition and the function of this matrix. In mesenchymal cells, the ECM can be conveniently divided into the pericellular matrix, close to or adjacent to the cell surface, and an intercellular matrix, which is more distant and surrounds the cell. The intercellular matrix can also form specialised structures, such as cartilage, tendon, and (with secondary deposition of calcium phosphate) bone and teeth. In addition, the matrix that underlies all epithelia and endothelia has a different chemical composition and organisation from the mesenchymal matrix, and is referred to as the basement membrane (Timpl and Brown, 1996). In the pre-molecular era of matrix research, the ECM was merely thought to provide inert scaffolding upon which cellular and tissue development could take place. It is now recognised that the ECM is a prerequisite for 73 74 G.J. Thomas & M. Davies the existence of multicellular organisms since it maintains tissue form and cellular polarisation, and also plays a pivotal role in a number of different cellular processes, including cell migration, cell growth and differentiation and wound healing. Also, different components of the ECM have been shown to act as antigens in immunopathological processes, and as defective components in certain pathological conditions.
eBook - PDF- Jan De Boer, Clemens van Blitterswijk, Peter Thomsen, Jeffrey Hubbell, Ranieri Cancedda, J.D. de Bruijn, Anders Lindahl, Jerome Sohier, David F. Williams(Authors)
- 2008(Publication Date)
- Academic Press(Publisher)
These molecules, mainly proteins, provide the mechanical strength required for proper function of each tissue and serve as a conduit for information exchange (i.e. signal-ing) between adjacent cells and between cells and the ECM itself. The ECM is in a state of dynamic reci-procity (Bissell and Aggeler, 1987) and will change in response to environmental cues such as hypoxia and mechanical loading. In the context of tissue engineer-ing applications therefore, use of the ECM as a scaf-fold indeed provides structural support, but perhaps more importantly provides a favorable environment for constructive remodeling of tissue and organs. 5.2.2 Composition The Extracellular Matrix represents a mixture of struc-tural and functional molecules organized in a three-dimensional architecture that is unique to each tissue. Most of these molecules are well-recognized and they form a complex mixture of proteins, glycosaminogly-cans, glycoproteins and small molecules arranged in a unique, tissue specific three-dimensional architecture (Laurie et al ., 1989; Baldwin, 1996; Martins-Green and Bissel, 1995). The logical division of the ECM into structural and functional components is not possible because many of these molecules have both structural and functional roles in health and disease. For example, both collagen and fibronectin, mol-ecules that once were considered to exist purely for their ‘structural’ properties, are now known to have a variety of ‘functional’ moieties with properties rang-ing from cell adhesion and motility to promotion of or inhibition of angiogenesis. These ‘bimodal’ or mul-tifunctional molecules provide a hint of the diverse occult amino acid sequences that exist within certain parent molecules and which, in themselves, harbor biologic activity. 5.2.2.1 Collagen Collagen is the most abundant protein within the mammalian ECM. Greater than 90% of the dry 5.2 Extracellular Matrix 123
eBook - PDFScaffolds for Tissue Engineering
Biological Design, Materials, and Fabrication
- Claudio Migliaresi, Antonella Motta, Claudio Migliaresi, Antonella Motta(Authors)
- 2014(Publication Date)
- Jenny Stanford Publishing(Publisher)
Physical, chemical, and mechanical properties of all body tissues depend on the composition and architecture of the Extracellular Matrix (ECM). Besides providing support and mechanical properties and being the reservoir of substances participating to the body metabolism, ECM is the microenvironment of cells, communicates with them with specific signaling molecules, and regulates their behavior and intercellular communications. ECM participates in cell activities, such as cell proliferation, adhesion, migration, differentiation showing a structure extremely Chapter 2 The Functional Role of Extracellular Matrix 978-981-4463-20-1 (Hardcover), 978-981-4463-21-8 (eBook) www.panstanford.com Eleonora Carletti, a, b, c Matteo Stoppato, a, b, c Claudio Migliaresi, a, b, c and Antonella Motta a, b, c a Department of Industrial Engineering and BIOtech Research Center, University of Trento, Trento, Italy b INSTM Research Unit, Trento, Italy c European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Trento, Italy [email protected] Eleonora Carletti and Matteo Stoppato have contributed equally to this work. 22 The Functional Role of Extracellular Matrix dynamic. Its components continuously undergo a remodeling process comprising deposition, degradation, and modifications, which are fundamental for the formation of the tissue architecture. The principal components of ECM comprehend a complex mixture of structural proteins, proteoglycans, and multi-adhesive matrix proteins that are produced intracellularly by resident cells, secreted into the ECM via exocytosis and finally assembled. The chapter reviews ECM composition and main functions, focusing in particular on ECM biochemical and physical properties and on the cell–ECM interactions. The role of ECM on the properties of some body tissues is described, and the mechanisms of ECM scarless healing in fetuses are compared with those occurring in adults.
- Edward Bittar(Author)
- 1996(Publication Date)
- Elsevier Science(Publisher)
Chapter 8 Extracellular Matrix D. W. L. HUKINS, S. A. WESTON, M. J. HUMPHRIES, and A. J. FREEMONT Introduction 182 Composition 184 CeU-Matrix Interactions 191 Cell Binding Sites in Adhesion Molecules 192 Receptor Identification 193 Regulation of Integrin Activity 195 Signal Transduction and Phenotypic Effects 196 Development 198 Aging Changes 201 Pathological Changes 205 Inflammation 205 Trauma 207 Neoplasia 207 Ischemia 208 Metabolic/Endocrine Disease 208 Specific Examples 209 Articular Cartilage 209 Bone 215 Skin 219 Microvasculature 224 Summary 227 Further Readings 227 Principles of Medical Biology, Volume 3 Cellular OrganeUes and the Extracellular Matrix, pages 181-232 Copyright © 1995 by JAI Press Inc. All rights of reproduction in any form reserved. ISBN: 1-55938-804-8 181 182 HUKINS, WESTON, HUMPHRIES, and FREEMONT INTRODUCTION The tissues and organs that make up the body are never composed solely of cells. Some tissues, such as brain, are densely packed with cells, but most, including skin, muscle and cartilage, contain large volumes of extracellular space filled by extracel-lular matrix (ECM). ECMs consist of hydrated assemblies of proteins and polysac-charides. They have mechanical functions and also influence the behavior of cells. The mechanical functions include packaging and protecting cells and tissues from external forces; in addition, some tissues, like tendons and bone, have important mechanical functions within the body. ECM can influence the behavior of cells in two ways. First, it provides a platform for cell movement and orientation; secondly, it signals to cells and thereby contributes to the regulation of tissue-specific gene expression. Understanding the structure of a tissue, the co-ordination of its func-tions, its creation during development, and its response to damage and disease, must therefore include an understanding of the function of its ECM. Most ECMs contain similar classes of macromolecules.
- Nikos Karamanos(Author)
- 2012(Publication Date)
- De Gruyter(Publisher)
1 An introduction to the Extracellular Matrix molecules and their importance in pathobiology and signaling 1.1 Extracellular Matrix: a functional scaffold Achilleas Theocharis, Chrisostomi Gialeli, Vincent Hascall, and Nikos K. Karamanos Tissues in mammals are made by cells but also contain significant quantities of support-ing matrices (i.e. extracellular mixtures of substances known as extracellular matrices [ECMs]). Cells must be properly supported and have contacts with neighboring cells and/or the ECM in order to function. ECMs are composed of a large variety of matrix macromolecules, including collagens, elastin, fibronectin (FN), laminins, tenascin, vi-tronectin, thrombospondin, secreted protein acidic and rich in cysteine (SPARC), vari-ous proteoglycans (PGs), and hyaluronan (HA). They are synthesized and secreted mainly by stromal cells, such as fibroblasts and osteoblasts, as well as immune cells and epithelial and endothelial cells. The ECMs of most tissues contain a set of related molecules interacting to form organized networks, adapted to the functional require-ments of the particular tissue (Frantz et al., 2010). Variability is to a large extent an effect of different assembly, partly regulated by a limited number of molecules more unique to a specific tissue. The major protein in the majority of ECMs is a fibril-forming collagen (i.e. collagen type I in most tissues and collagen type II in cartilage-related tissues). These collagens form fibrillar structures, and the process is tuned by other fibrillar collagens (e.g. col-lagen type V with type I and collagen type XI with type II) that are present in small amounts in the fibers. Fibril formation is further regulated by a number of other ECM proteins, such as members of the small leucine-rich repeat (SLRP) PG family (decorin, biglycan, fibromodulin, and lumican) as well as the thrombospondins, the matrilins, and many others.
- Michael J. Yaszemski, Debra J. Trantolo, Kai-Uwe Lewandrowski, Vasif Hasirci, David E. Altobelli, Donald L. Wise(Authors)
- 2003(Publication Date)
- CRC Press(Publisher)
Cell-ECM interactions participate directly in promoting cell adhesion, migration, growth, differentiation, and programmed cell death; in modulation of the activities of cytokines and growth factors, and in directly activating intracellular signaling. All these activities are connected in some way to biological compatibility. The molecular complex called ECM has as basic components collagens and other glycopro- teins implicated also in the resistance to tensile and compressive mechanical forces. The macromolecular components of the polymeric assemblies of the ECM are in many cases secreted by cells as precursor molecules that are significantly modified (proteolysis pro- cessed, sulfated, oxidized, and cross-linked) before they assemble with other components onto functional polymers [8]. The formation of matrix assemblies in vivo is therefore in most instances a unidirectional, irreversible process, and the disassembly of the matrix is not a simple reversal of assembly, but involves multiple, highly regulated processes. One consequence of this is that polymers reconstituted in the laboratory with components extracted from extracellular matrices do not have all the properties they have when assembled by cells in vivo. DOI: 10.1201/9780203913338-1 2 Cannas et al. The ECM in vivo is also modified by cells as they proliferate, differentiate, and migrate, and cells in turn continuously interact with the matrix and communicate with each other through it (Fig. 1)[9]. The ECM is therefore not an inert product of secretory activities, but influences cellular shape, fate, and metabolism in ways that are as important to tissue and organ structure and function as the effects of many cytoplasmic processes.
eBook - ePub- Clemens van Blitterswijk, Jan De Boer(Authors)
- 2014(Publication Date)
- Academic Press(Publisher)
5.2. Native Extracellular Matrix
The ECM represents the secreted products of cells in all tissues and organs. ECM composition is generally conserved across tissue types; however, there exists a unique, tissue-specific, and three-dimensional ultrastructure. The structural and functional molecules that comprise the ECM provide the mechanical properties necessary for proper functioning of each tissue, and facilitate signal transduction between adjacent cells and between cells and the ECM itself. The ECM fluctuates in response to changes in microenvironmental cues including cellular activity and mechanical loading, and therefore is considered to be in a state of dynamic reciprocity with the cells and factors that influence the ECM (Bissell and Aggeler, 1987 ).Figure 5.1 Schematic representation of the assembly of collagen I. (a) Individual collagen polypeptide chains. The polypeptides consist of the repeating sequence Gly-X-Y, where X is often proline and Y is often hydroxyproline; (b) collagen is made up of three polypeptide strands which are all left-handed helixes and twist together to form a right-handed coiled coil. The polypeptide strands are synthesized as precursor chains with propeptides (globular extensions) on the C and N ends. The propeptides are cleaved into short nonhelical telopeptides; (c) collagen molecules self-assemble into collagen fibrils; (d) collagen fibers are formed by end-to-end and lateral assembly of collagen fibrils, resulting in a regular banding pattern that is characteristic of collagen.5.2.1. ECM Composition
The ECM is composed of a complex combination of proteins including structural molecules such as collagen, fibronectin, and laminin, as well as functional molecules such as glycosaminoglycans (GAGs) and growth factors all arranged in a tissue-specific three-dimensional ultrastructure (Badylak, 2005
eBook - PDF- John P. Fisher, Antonios G. Mikos, Joseph D. Bronzino(Authors)
- 2007(Publication Date)
- CRC Press(Publisher)
This chapter will focus on key ECM components and their functions, emphasizing relationships between natural matrices present in both hard and soft tissues and cell function. The concept of “mining” the natural matrix for active motifs that are useful in tissue 3 -1 3 -2 Tissue Engineering engineering applications also is introduced. Finally, the utility of translating knowledge gained from study of native ECM to controlled delivery of growth factors and deliberate modulation of cell and tissue phenotype for engineering purposes is discussed. 3.2 ECM and Functional Integration of Implanted Materials Cells sense and respond to a variety of signals that include those that are soluble such as growth factors, differentiation factors, cytokines, and ion gradients. In addition, cell behavior and phenotype is governed by responses to other types of signals that include mechanical forces, electrical stimuli, and various physical cues. Immobilized protein matrices that generally are fixed in space also regulate cell function. The general term that has come to denote the complex mixture of proteins on the outside of cells that governs their behavior is ECM. Evolution has provided cells with surface receptors to ECM components that enable them to recognize and decipher the signals that they encounter from the ECM and which influence cell growth, division, and differentiation [1]. For descriptive purposes, cell adhesion is classified into categories of cell–substratum and cell–cell attachment. Cell–cell interactions may occur between like cells (homotypic events) or between dissimilar cells (heterotypic). Homotypic interactions stabilize epithelia, which typically lie upon a sheet of special-ized ECM called the basement membrane, discussed in Section 3.2. Heterotypic interactions govern many normal cellular phenomena including embryo–uterine implantation, immune surveillance, cell migration during embryogenesis, and neurotransmission.
eBook - ePub- Clemens van Blitterswijk, Jan De Boer, Clemens Van Blitterswijk(Authors)
- 2022(Publication Date)
- Academic Press(Publisher)
Chapter 5: Extracellular Matrix as a bioscaffold for tissue engineering
Brian M. Sicari1, Ricardo Londono1, Jenna L. Dziki1,2, and Stephen F. Badylak1,2,31 McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, United States2 Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States3 Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, United StatesAbstract
This chapter discusses mammalian Extracellular Matrix (ECM) as a biologic scaffold material for tissue engineering applications. ECM has been used as a surgically implantable bioscaffold for the reconstruction of injured or missing tissues. Biologic scaffolds composed of ECM alter the default mammalian injury response and promote constructive and functional tissue remodeling. This chapter reviews ECM bioscaffold preparation and mechanisms of action. Commercially available ECM bioscaffolds and recent clinical applications are also discussed.Keywords
Biologic scaffolds; ECM bioscaffolds; Extracellular Matrix (ECM); Regenerative medicine; Tissue engineering; Tissue remodeling5.1. Learning objectives
After reading this chapter you will be able to:- ▪ Understand the composition, ultrastructure, and physical properties of mammalian Extracellular Matrix (ECM).
- ▪ Recognize the utility of bioscaffolds derived from ECM in the field of tissue engineering.
- ▪ Understand the process by which ECM bioscaffolds are manufactured.
- ▪ Understand the meaning of “constructive tissue remodeling.”
- ▪ Identify mechanisms behind constructive tissue remodeling facilitated by ECM bioscaffolds.
- ▪ Recognize clinical applications of ECM bioscaffolds.
The whole idea about Regenerative Medicine is not to make us live forever, is quality [of life] over quantity. S. Badylak, TEDx conference, 2019The field of Regenerative Medicine exists because we are not very good at treating some very common and serious injuries in people. S. Badylak, 20125.2. Introduction
eBook - PDF- Edward Bittar(Author)
- 1998(Publication Date)
- Elsevier Science(Publisher)
Chapter 5 The Role of Extracellular Matrix during Development ESMOND J. SANDERS Introduction 89 The Molecules of the Extracellular Matrix 90 Proteoglycans 90 Collagens 92 Fibronectin 93 Laminin 94 Tenascin/Cytotactin 95 Integrins 95 Cellular Interactions with the Extracellular Matrix in Development 97 Cell Attachment and Cell Movement 97 Cell Differentiation 99 Summary 99 INTRODUCTION The extracellular environment of cells in developing embryos is not merely a pas- sive supporting scaffolding or connective tissue. Instead, the matrix in which the Principles of Medical Biology, Volume 11 Developmental Biology, pages 89-101. Copyright 9 1998 by JAI Press Inc. All rights of reproduction in any form reserved. ISBN: 1-55938-816-1 89 90 ESMOND I. SANDERS cells are embedded exerts profound influences on both cell movement and cell dif- ferentiation in embryos. During development, cells migrate or rearrange their posi- tions relative to one another, and these movements, of which there are many examples, are initiated at specific times in development, are often highly directed, and cease at precise times and locations. The precision of these movements is thought to be generated by programmed changes in the activity of the cytoskeleton in combination with changes in the ability of cells to interact with elements of their extracellular environment (Sanders, 1989; Damsky et al., 1993). This extracellular environment, consisting of a matrix of primarily proteins and glycoproteins, is it- self constantly changing, providing developmentally regulated cues for movement to which the matrix receptors present on the cell surface can respond. The interac- tion between the Extracellular Matrix and the receptors is then thought to activate the cytoskeleton and thereby initiate or inhibit cell movement. The Extracellular Matrix may also regulate cell differentiation independently of cell migration or cell shape changes.
- Inamuddin, Abdullah M. Asiri, Ali Mohammad, Dr. Inamuddin(Authors)
- 2018(Publication Date)
- Woodhead Publishing(Publisher)
The dynamic interaction between biochemical processes and biomechanical signaling is crucial during various physiological and biological processes, such as embryogenesis, morphogenesis, wound healing, and cellular behaviors. It also plays important rule in pathological processes, such as tumor development and metastasis. The cells continuously interact with surrounding ECM and substrate during these processes, and the feedback signals play a crucial role to define cellular behaviors [81]. It has been demonstrated by various studies that the ECM provides an instructive environment for stem cells, as well as other local cells. This is achieved by ECM unique biomechanical and biochemical properties and the dynamic interplay between cells and ECM. The importance of ECM nanotopography and rigidity in enhancing the proliferation and inducing the differentiation of stem cells has also been highlighted. All of these aspects are dynamically orchestrated to provide instructive cues for physiological cell behavior. The studies involving the interaction of stem cells and ECM will open new horizons as they allow more accurate mimicking of essential properties of in vivo niches by synthesizing and designing instructive and smart in vitro systems. Alternatively, these tissue-specific extracellular networks can act as a nanocomposite scaffold for hosting, maintaining, and directing various stem cells activities [ 124 – 126 ]. Further in vitro studies together with in vivo applications of these engineered biomaterials can open new scope to improve the knowledge of stem cell biology and develop new areas in cell-based therapy and tissue engineering. References [1] Hynes R.O. The Extracellular Matrix: not just pretty fibrils. Science. 2009;326:1216–1219. doi:10.1126/science.1176009. [2] Lu P., Takai K., Weaver V.M., Werb Z. Extracellular Matrix degradation and remodeling in development and disease. Cold Spring Harb. Perspect
- Francesco Travascio(Author)
- 2016(Publication Date)
- IntechOpen(Publisher)
Journal Controlled Release. 2013;172(3):782–94. [72] Bertrand N, Wu J, Xu X, Kamaly N, Farokhzad OC. Cancer nanotechnology: the impact of passive and active targeting in the era of modern cancer biology. Advanced Drug Delivery Reviews. 2014;66:2–25. Biophysical Properties of the Basal Lamina: A Highly Selective Extracellular Matrix http://dx.doi.org/10.5772/62519 221 Chapter 10 The Role of Extracellular Matrix Proteins in the Urinary Tract: A Literature Review Cevdet Kaya and Bahadır Şahin Additional information is available at the end of the chapter http://dx.doi.org/10.5772/62807 Abstract The Extracellular Matrix (ECM) is a noncellular component with a crucial role on tissue morphogenesis, differentiation and hemostasis within all tissues and organs. With advancement in the technology and increased data on ECM components, it was realized that many conditions in urinary tract have a close relation with the composition of ECM in the affected tissue. According to some basic research studies, ECM composition may give us important information about the prognosis and progression of disease in addition to the cause and pathophysiology of the diseases such as congenital ureterovesical and ureteropelvic junction obstruction. Afterwards, with better understanding of ECM one can develop new treatment and follow-up models. This chapter will summarize the evidence-based role of ECM in urinary tract conditions. Keywords: urinary tract, Extracellular Matrix, immunohistochemistry, ureteropelvic junction, ureterovesical junction 1. Extracellular Matrix The Extracellular Matrix (ECM) is a noncellular component within all tissues and organs, and it is essential for the scaffolding of cellular constituents and also it plays a crucial role on tissue morphogenesis, differentiation and hemostasis [1]. It is an anchoring platform for epithelia, forms the basement membrane, and also surrounds capillaries and neural cells, and is part of the connective tissue [2].
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