Extracellular Matrix and Wound Healing

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Today's Topic: Extracellular Matrix (ECM).
Exam 4: Scheduled for next week covering:
- Mitochondria
- Signal Transduction
- Today's lecture on ECM.
Next Class (Thursday): Will focus on material for Exam 5 (not included in Exam 4).

Context: Shift from intracellular focus to the extracellular environment surrounding cells.
Key Statement: "Half the secrets of the cell are actually outside the cell." - Dr. Mina Bissell (2007)
- Emphasizes the importance of understanding interactions outside the cell.

Cell
Tissues: Formed by groups of cells.
Organs: Composed of multiple tissue types.
Organ Systems: Contains organs that function together (e.g., circulatory system).
- Inclusion of Tissues: Blood considered a tissue, highlighting complex connectivity in biological systems.

Extracellular Matrix (ECM):
- A three-dimensional network of macromolecules surrounding cells.
- Provides structural support and biochemical support, facilitating signal transduction from extracellular to intracellular environments.

Illustration of ECM: Visual includes cytoskeleton and biomembrane elements.
- Collagen and Fibronectin as two major ECM components, distinguishable in histological staining (green = collagen, blue = fibronectin).

Plants vs. Animals:
- Plants: Have rigid cell walls made of cellulose, providing strong protective structures.
- Cellulose: A polysaccharide; contributes to crunch in vegetables.
- Middle Lamella: Sticky layer aiding cell adhesion, primarily composed of sugars and proteins.
- Animals: Evolved a flexible ECM to allow mobility and structural integrity for active lifestyles.
- Includes components like collagen and proteoglycans to offer strength and flexibility.

Provides flexibility and strength:
- Acts as a protective barrier around tissues without sacrificing flexibility (e.g., blood vessels retain shape).
- Compartmentalizes tissues allowing for functional separation (different tissues, functions).
Bones: Composed of calcified extracellular matrix providing rigid structure through mineral deposition.
Involved in cell communication and movement, and during wound healing processes, allowing cellular migration.

Connective Tissue:
- General role: Holds structures together.
- Examples: Adipose (fat), cartilage, tendons, bone, blood.
Muscle, Epithelial, Neural Tissues:
- Minimal ECM presence in comparison to connective tissues.
- Epithelial tissue: Basal lamina as a specific form of ECM underneath epithelial layers.

Loose vs. Dense Connective Tissues:
- Loose Connective Tissue: Contains a high ratio of ground substance (e.g., adipose tissue).
- Dense Connective Tissue: Lower ratio of ground substance, e.g., tendons and ligaments.

Definition: Liquid component within the ECM, which includes a mixture of sugars and proteins.
Function: Determines tissue density (loose vs. dense).

Types:
- Collagen: Long polypeptide chains forming fibers; critical in tissue structure and integrity.
- Elastin: Provides elasticity needed for tissue flexibility.

Composition: Heterotrimer structure, composed of glycine (repeats every third amino acid) and proline.
Collagen’s Structural Importance:
- Forms strong, insoluble fibers not readily absorbed by surrounding fluid.
Modification: Hydroxylation of proline and lysines important for structural stability and interactions post-translation.

Pre-collagen: Synthesized in the nucleus with subsequent post-translational modifications occurring in the ER and Golgi.
Procollagen: Processed and secreted form prior to functional collagen formation.
- Cleavage of N- and C- terminals occurs outside of the cell, transitioning procollagen to a functional collagen fibril.

Structure:
- Tropoelastin (pre-elastin) is synthesized and modified similarly to collagen.
- Important components: Coil region for flexibility, hinge region for protein-protein interactions.
Linking Mechanism: Desmason crosslinks formed between elastin molecules enable elasticity.

Functionality: Facilitate cell-cell interactions and contribute to overall structural organization of ECM.
** Examples**:
- Fibronectin: Links ECM with cell membranes, pivotal for signaling.
- Integrin: Transmembrane protein crucial for signal transduction connecting inside and outside the cell.
- Laminin: Cross-shaped glycoprotein important for epithelial cell adhesion beneath the cell layers.

Definition: Long, negatively charged polysaccharides that attract and retain water, pivotal in cartilage and connective tissues.
Structure & Function:
- Consists of disaccharides, typically containing an amino sugar.
- Provides shock-absorbing qualities when hydrated, balancing fluid within tissues.

Four Overlapping Processes:
- Hemostasis: Initial response stops bleeding through platelet aggregation and temporary plug formation.
- Inflammation: Activation of immune response; recruiting white blood cells for debris removal.
- Proliferation: Tissue growth and replacement; recruitment of fibroblasts to synthesize new ECM.
- Remodeling: Formation of scar tissue; myofibroblasts contract to augment the scar strength.

Fibroblasts synthesis ECM to complete the wound closure.
Growth factors are critical in all stages for recruiting required cells and promoting healing.
Scar maturation over time results in stronger tissues but not typically replacement or shedding of scar tissue.

The Role of Platelets: Release of growth factors facilitating wound healing initiation and transition through the different processes of healing.
Water retention and fluid accumulation during inflammation as a physiological response to injury.