Extracellular matrix, extracellular polysaccharides and proteins (collagen, elastin) - structure, properties, function. Metabolism of collagen.

Introduction

The extracellular matrix (ECM) is a complex network of macromolecules secreted by cells, especially fibroblasts. It provides structural and biochemical support to surrounding tissues. The ECM is composed of fibrous proteins, proteoglycans, glycosaminoglycans (GAGs), and adhesive glycoproteins. Two major structural proteins of the ECM are collagen and elastin.

Components of the Extracellular Matrix

- **Glycosaminoglycans (GAGs)**: Linear polysaccharides composed of repeating disaccharide units. Types include hyaluronic acid, chondroitin sulfate, dermatan sulfate, heparan sulfate, and keratan sulfate. They are highly negatively charged and retain water, contributing to tissue hydration and resilience.

- **Proteoglycans**: Consist of a core protein covalently linked to GAGs. They form a gel-like matrix that resists compression and facilitates diffusion.

- **Adhesive glycoproteins**: Such as fibronectin and laminin, they connect ECM components and mediate cell-ECM interactions.

Collagen: Structure, Properties, and Function

Collagen is the most abundant protein in the human body. It provides tensile strength and structural integrity to connective tissues such as skin, tendons, ligaments, cartilage, and bones.

Structure:

- Triple helical structure composed of three α-chains.

- Rich in glycine, proline, and hydroxyproline.

collagen fibers

- Collagen types I, II, III, and IV are the most common.

Functions:

- Provides mechanical strength.

- Supports tissue architecture.

- Plays a role in cell adhesion, migration, and differentiation.

Metabolism of Collagen

Collagen biosynthesis is a multistep process:

1. **Transcription and Translation**: Synthesis of preprocollagen in the rough ER.

2. **Post-translational Modifications**:

  - Hydroxylation of proline and lysine (requires vitamin C).

  - Glycosylation of hydroxylysine.

3. **Formation of Triple Helix**: Procollagen is formed and secreted into the extracellular space.

4. **Cleavage and Cross-linking**: Procollagen is cleaved to tropocollagen and cross-linked by lysyl oxidase (requires copper) to form collagen fibrils.

Degradation:

- Performed by collagenases (matrix metalloproteinases) during tissue remodeling.

Elastin: Structure, Properties, and Function

Elastin is a highly elastic protein found in tissues that require recoil, such as lungs, arteries, and skin.

Structure:

- Composed of tropoelastin monomers cross-linked by desmosine and isodesmosine.

Aorta - elastin stain

- Rich in non-polar amino acids like glycine, valine, alanine.

Function:

- Provides elasticity and resilience.

- Maintains structural integrity under stretch and recoil cycles.

Conclusion

The extracellular matrix is critical for structural support, cellular communication, and tissue development. Collagen and elastin, as major ECM proteins, are essential for the mechanical properties of connective tissues. Disruption in ECM synthesis or metabolism can lead to pathological conditions such as scurvy, fibrosis, or connective tissue disorders.

References

1. Guyton and Hall Textbook of Medical Physiology, 14th Edition

2. Lehninger Principles of Biochemistry, 7th Edition

3. Lippincott Illustrated Reviews: Biochemistry, 7th Edition