KN

Unit 08 Pt3

Extracellular Matrix (ECM) Overview

  • Definition: The extracellular matrix is a molecular network surrounding cells in tissues, influencing their properties and functions.

  • Composition: Comprised mainly of proteins produced by local cells, distinctively abundant in connective tissue compared to surrounding cells.

Functions of the Extracellular Matrix

  • Support: Provides structural integrity to tissues.

  • Regulatory Functions:

    • Important for cell survival, migration, and proliferation.

    • Plays a critical role in tissue and organ development.

Basal Lamina

  • Definition: A specialized type of ECM primarily found in epithelial tissues.

  • Components: Includes glycoproteins like laminin, type IV collagen, nitrogen, and proteoglycans like perlecan.

Key Cell Types Associated with ECM

  • Fibroblasts: Predominant in connective tissue.

  • Chondroblasts: Found in cartilage.

  • Osteoblasts: Involved in bone formation.

Proteoglycans and Glycosaminoglycans (GAGs)

  • Proteoglycans:

    • Composed of a small protein core attached to various GAGs.

    • Form hydrated gel-like substances that resist compression but permit diffusion (important in tendons and bones).

  • Glycosaminoglycans:

    • Unbranched polysaccharides made of repeating disaccharide units (sugars like GlcNAc or GalNAc and uronic acid).

    • Highly negatively charged due to sulfation, attracting water and cations (e.g., sodium).

Major Types of Glycosaminoglycans

  • Hyaluronan:

    • Simplest and non-sulfated GAG, consists of 25,000 disaccharide units.

    • Key in embryonic development and wound healing.

  • Chondroitin sulfate, Dermatan sulfate, Heparan sulfate, Keratan sulfate: Other types with specific properties and functions.

Collagen: The Principal ECM Protein

  • Overview: Most abundant protein (25% body protein); main component of skin and bone.

  • Structure: Long, stiff triple helix formed by three alpha chains providing tensile strength.

  • Important Types:

    • Type I: Common in skin and bone, forms long fibrils.

    • Type IV: Major component of the basal lamina.

    • Types IX and XII: Fibro-associated collagens, help organize collagen fibrils.

Collagen Synthesis

  • Occurs in the endoplasmic reticulum (ER) with hydroxylation of proline and lysine.

  • Collagen is synthesized as a propeptide to prevent premature aggregation.

  • After vesicular transport, collagen is secreted, cleaved, and self-assembles into fibrils outside cell.

  • Turnover: Continuous degradation and synthesis cycle, important for tissue maintenance.

  • Deficiencies: Example includes Scurvy (vitamin C deficiency) leading to fragile blood vessels and weakened tissues.

Diseases Related to Collagen

  • Inherited disorders such as Osteogenesis Imperfecta and Ehlers-Danlos syndrome caused by mutations affecting collagen synthesis or structure.

Elastic Fibers in the ECM

  • Function: Provide resilience and recoil, critical in tissues like lung, skin, and blood vessels.

  • Major Component: Elastin, highly hydrophobic and rich in proline and glycine.

    • Cross-linked structure allows for spring-like properties.

  • Associated Components: Microfibrils (e.g., fibrillin) support elastin and maintain integrity of elastic fibers.

  • Diseases: Mutations can lead to Marfan syndrome, which risks arterial issues.

Fibronectin

  • Exists in soluble form in bodily fluids or as insoluble fibrils in the ECM.

  • Fibrils are formed through disulfide bonds and are integral for cell adhesion.

  • Binding Proteins: Integrins link fibronectin to the intracellular actin cytoskeleton, aiding cell interactions with the ECM.

Summary

The ECM is a complex structure critical for tissue integrity and function, composed of various proteins, cell types, and includes specialized components like collagen and elastin. Understanding the ECM's structure and function is essential for comprehending tissue biology and associated diseases.