Overview
This lecture covers the structure, components, and functions of the extracellular matrix (ECM), focusing on its major macromolecules, associated proteins, and related diseases.
Introduction to Extracellular Matrix (ECM)
- The ECM is a non-cellular, three-dimensional network of macromolecules surrounding cells.
- ECM composition varies by tissue and includes structural proteins, specialized proteins, and proteoglycans.
Functions of the ECM
- Provides mechanical support for cell anchorage, migration, and maintenance of cell polarity.
- Regulates cell growth via integrin-mediated signaling.
- Maintains cell differentiation, morphogenesis, and tissue homeostasis.
- Acts as a scaffold for tissue renewal and regeneration.
Main Components of ECM
- Fibrous structural proteins: Collagen and elastin give tensile strength and elasticity.
- Adhesive glycoproteins: Fibronectin and laminin link matrix elements and cells.
- Water-hydrated gels: Proteoglycans and hyaluronic acid offer resilience and lubrication.
Collagen
- Collagen is the most abundant ECM protein, making up about 30% of the body's protein mass.
- Over 30 collagen types exist; divided into fibrillar (fibril-forming) and nonfibrillar collagens.
- Fibrillar collagens provide structural support; nonfibrillar collagens form flexible networks (e.g., type IV in basement membranes).
- Collagen cross-linking increases with glycation, forming AGEs, contributing to vessel wall diseases and inflammation.
- Osteogenesis imperfecta results from reduced type I collagen due to gene mutation.
Noncollagenous Proteins
- Elastin provides elasticity and recoil in tissues like lungs and arteries.
- Tropoelastin is elastin's soluble precursor; mutations or enzymatic digestion (e.g., by elastase) cause diseases like emphysema.
- Fibrillin forms microfibrils for elastin deposition and is essential for ECM structural integrity.
Specialized Glycoproteins
- Fibronectin: ECM and plasma glycoprotein involved in cell adhesion and migration, contains RGD sequence for integrin binding.
- Laminin: Basement membrane glycoprotein, forms cross-shaped molecules, binds cells, collagen IV, and other ECM proteins via nidogen and perlecan.
Proteoglycans and Glycosaminoglycans (GAGs)
- Proteoglycans consist of core proteins with covalently bound GAGs, forming hydrated gel matrices.
- GAGs are long, linear polysaccharides with repeating disaccharide units, often sulfated or acetylated.
- Aggrecan in cartilage provides rigidity and structural support via association with hyaluronic acid and link proteins.
- Proteoglycans are degraded in lysosomes by proteases and hydrolases.
Key Terms & Definitions
- ECM (Extracellular Matrix) — Non-cellular network of macromolecules surrounding and supporting cells.
- Collagen — Main structural ECM protein, provides strength.
- Elastin — Protein enabling tissue elasticity and recoil.
- Fibronectin — Adhesive glycoprotein linking ECM components and cells.
- Laminin — Basement membrane glycoprotein linking cells and ECM.
- Proteoglycan — Core protein with GAG side chains, forms hydrated ECM gel.
- Glycosaminoglycan (GAG) — Linear polysaccharide, component of proteoglycans.
- AGE (Advanced Glycation End Product) — Cross-linked proteins increased by glycation, linked to pathology.
Action Items / Next Steps
- Review the types and functions of ECM components.
- Study diseases associated with ECM protein mutations (e.g., osteogenesis imperfecta, Goodpasture's syndrome).
- Prepare for discussion on ECM remodeling and clinical implications.