Definition: The ECM is a macromolecular network produced by cells that provides structural and biochemical support to surrounding cells.
Components of ECM:
Various classes of molecules specific to different tissues.
Commonly found in connective tissues, produced primarily by fibroblasts (CT), chondroblasts (cartilage), and osteoblasts (bone).
Plays crucial roles in support, regulation, survival, development, migration, proliferation, shape, and function of tissues.
Basal Lamina: A specialized ECM in epithelial tissues crucial for allowing cell functions and interactions.
Composition of ECM
Proteoglycans: Composed of glycosaminoglycan (GAG) chains linked to core proteins.
Function: Forms hydrated gels, provides resistance to compression, facilitates diffusion in tissues.
Collagens: Major protein in ECM, making up about 25% of total protein mass.
Function: Provides tensile strength and structural integrity to tissues.
Elastin: Contributes to the elasticity of tissues like skin and blood vessels.
Fibronectin: A multidomain glycoprotein that assists in organizing the ECM and binds to integrins, facilitating cell-ECM interactions.
Glycosaminoglycans (GAGs)
Structure: Long unbranched polysaccharide chains made of repeating disaccharides, usually sulfated.
Types:
Hyaluronan
Chondroitin sulfate
Dermatan sulfate
Heparan sulfate
Keratan sulfate
Role in ECM: Occupy large volumes, form hydrated gels, attract cations and water, contributing to turgor and compressive strength.
Linking GAGs to Core Proteins
Hyaluronan: Simplest GAG, abundant in developing tissues and wound healing. Not sulfated and not typically linked to core proteins.
Other GAGs: Synthesized in the cell, linked to core proteins in the ER and Golgi, can be extensively modified (sulfation).
Proteoglycan Diversity
Core Proteins: Can vary widely; examples include aggrecan (with over 100 GAGs) and decorin (with 1 GAG).
Proteoglycans can form larger aggregates (e.g., aggrecan with hyaluronan).
Collagen Structure and Function
Types of Collagen:
Type I: Most abundant; found in skin and bone, forms fibrils and cable-like bundles.
Type IV: Network-forming; major component of basal lamina.
Types IX and XII: Fibril-associated collagens that help organize the fibrils.
Collagen Assembly: Helix stabilizes through hydrogen bonding, pro-peptides prevent premature fibril formation; self-assembly occurs near the cell surface.
Diseases Related to Collagen Defects
Scurvy: Caused by vitamin C deficiency affecting collagen synthesis, leading to fragile blood vessels and slow healing.
Osteogenesis Imperfecta: Genetic disorder caused by defective collagen, leading to brittle bones.
Ehlers-Danlos Syndrome: Results in fragile skin and joints due to collagen abnormalities.
Elastic Fibers in ECM
Function: Provide elasticity and allow tissues to recoil after being stretched.
Composed of elastin and microfibrils (e.g., fibrillin), necessary for structural integrity.
Elastin Characteristics: Highly hydrophobic, rich in proline and glycine, reversibly stretches and recoils due to its molecular structure.
Fibronectin and Its Role
Soluble vs. Insoluble form: Fibronectin can exist in soluble form in body fluids or as part of insoluble fibrils in the ECM.
Interaction with Cells: Fibronectin binds to integrins on cell surfaces, linking the ECM to the cytoskeleton, which helps transmit mechanical signals and organize extracellular structures.