The extracellular matrix (ECM) is the non-cellular component of tissues, providing structural support and influencing cell behavior. It's composed of diverse proteins and molecules, each with unique functions. Collagen, elastin, proteoglycans, and glycoproteins work together to create a dynamic environment.

ECM organization varies between tissues, with basement membranes and interstitial matrices serving different roles. The matrix constantly undergoes remodeling, playing crucial parts in development, wound healing, and disease processes. Understanding ECM components and functions is key to grasping tissue biology and pathology.

Extracellular Matrix Components

Components of extracellular matrix

• Collagen
  • Most abundant protein in ECM
  • Provides tensile strength and structural support to tissues (skin, bone, tendons)
  • Multiple types exist with different functions (Type I in skin, Type II in cartilage, Type IV in basement membranes)
• Elastin
  • Provides elasticity and resilience allowing tissues to stretch and recoil (blood vessels, lungs)
  • Composed of tropoelastin monomers cross-linked by lysyl oxidase
• Proteoglycans
  • Consist of a core protein with attached glycosaminoglycan (GAG) chains (heparan sulfate, chondroitin sulfate)
  • GAGs are highly negatively charged and hydrophilic attracting water molecules
  • Provide hydration, cushioning, and binding sites for growth factors (aggrecan in cartilage, versican in blood vessels)
• Glycoproteins
  • Proteins with covalently attached carbohydrate chains
  • Facilitate cell-matrix interactions and cell signaling (fibronectin, laminin)
  • Help organize and stabilize ECM structure (nidogen, tenascin)

Assembly of extracellular matrix

• Cells secrete ECM components into extracellular space (fibroblasts, chondrocytes, osteoblasts)
• Collagen assembly involves:
  1. Synthesis and processing of procollagen molecules in endoplasmic reticulum and Golgi apparatus
  2. Secretion and cleavage of procollagen by proteases to form tropocollagen
  3. Self-assembly of tropocollagen into collagen fibrils and fibers
• Elastin assembly involves:
  1. Synthesis and secretion of tropoelastin monomers by cells
  2. Cross-linking of tropoelastin monomers by lysyl oxidase to form elastic fibers
• Proteoglycans and glycoproteins interact with collagen and elastin fibers helping organize and stabilize ECM structure
• Cells continually synthesize, degrade, and reorganize ECM components through:
  • Matrix metalloproteinases (MMPs) which degrade ECM components
  • Tissue inhibitors of metalloproteinases (TIMPs) which regulate MMP activity

Extracellular Matrix Organization and Function

Basement membrane vs interstitial matrix

• Basement membrane
  • Thin, sheet-like structure separating epithelial, endothelial, and muscle cells from underlying connective tissue
  • Composed primarily of Type IV collagen, laminin, and heparan sulfate proteoglycans
  • Provides structural support and influences cell behavior (polarity, differentiation, migration)
• Interstitial matrix
  • Occupies space between cells in connective tissues (dermis, bone, cartilage)
  • Composed of fibrillar collagens (Types I, II, III), elastin, proteoglycans, and glycoproteins
  • Provides structural support, mechanical properties, and reservoir for growth factors and cytokines
  • Composition varies depending on tissue type and function

Remodeling of extracellular matrix

• Physiological processes involving ECM remodeling:
  • Embryonic development and morphogenesis
  • Tissue repair and wound healing
  • Angiogenesis forming new blood vessels
  • Bone remodeling and homeostasis
• Pathological processes involving ECM remodeling:
  • Fibrosis with excessive ECM deposition in response to chronic inflammation or tissue injury leading to organ dysfunction (liver cirrhosis, pulmonary fibrosis)
  • Cancer where ECM remodeling facilitates tumor growth, invasion, and metastasis and altered ECM composition and stiffness influence cancer cell behavior
  • Arthritis involving degradation of articular cartilage ECM leading to joint damage and pain with imbalance between MMPs and TIMPs
  • Cardiovascular diseases where ECM remodeling in blood vessels can lead to atherosclerosis and plaque rupture and myocardial ECM alterations can contribute to heart failure