EXTRACELLULAR MATRIX(pp 9-17)

Extracellular Matrix (ECM)

• Apart from specific cells, tissues contain matrix of macromolecules in the extracellular space- Extracellular Matrix.

• ECM is secreted by cells that live within the tissue.

• Usually they are proteins and carbohydrates that are secreted by cells and assembled into an organized meshwork.

• ECM is specialized to perform different functions in different tissues.

Functions• Provides support and anchorage for cells.

• Regulates and determine cells dynamic behavior :- cell differentiation- adhesion- migration

• Provides mechanical support for tissues and organ architecture

- growth- regenerative and healing processes - determination and maintenance of the structure

• Place for active exchange of different metabolites, ions, water.

Components of ECM• Three categories of extracellular macromolecules make up ECM:

• PROTEOGLYCANS: Aggregates of protein and glycoaminoglycans (GAGs).

• FIBROUS PROTEINS: Collagen and Elastin which are the major components.

• ADHESIVE PROTEINS: Fibronectin and laminin are glycoproteins.

Proteoglycans• They are aggregates of protein and GAGs.• Glycosaminoglycans (GAG) are negatively

charged complex carbohydrates.

• Due to negative charge, ECM with GAGs floods with water creating turgor pressurehelping ECM to resist opposing forces of tissue compression.

• Synovial fluid is also rich in GAGs which on compression release all the water they are holding and on release of all the pressure they again bind to large amount of water.

• This change in hydration of ECM is referred to as resilience.

Proteoglycans Structure

• GAGs are covalently attached to protein and form proteoglycan monomers.

• Monomer has core protein with GAGs extending, giving the resulting proteoglycan as having bottle brush appearance.

• Individual monomers then associate with large GAG to form proteoglycan aggregates.

• The core protein and the large GAG is stabilized by smaller link proteins.

PROTEOGLYCAN

Fibrous Protein-Collagen• Fibrous proteins are extended molecules that serve structural

function in tissues.• Collagen and elastin are the fibrous proteins in the ECM.

• COLLAGEN: The most abundant protein in the body, making 25%-35% of all the whole-body proteins.

• Collagen contributes to the stability of tissues and organs.

• It maintains their structural integrity. • It has great tensile strength.

• The main component of cartilage, ligaments, tendons, bone and skin.

• Plays an important role in cell differentiation, movement.

• Plays an important role in tissue and organ development.

• STRUCTURE: They are composed of three helical protein α chains that wind around one another forming triple helix.

• Various types of collagen have different α chains.

• Glycine and proline are the main amino acids.

Fibrous Protein-Collagen

SYNTHESIS: 3 alpha chains à Procollagen• Procollagen secreted from cells• Procollagen peptidase cleaves ends to form

collagen• Collagen molecules assemble to form fibrils• Fibrils assemble into fibers.

Fibrous Protein-Collagen

Fibrous Protein-Elastin• Elastic fibers formed by elastin enable skin, arteries and lungs to

stretch and recoil without tearing.

• SNYTHESIS: Cells secrete tropoelastin in the extracellular space.

• Tropoelastin interacts with fibrillin.

• Lysine (amino acid) in tropoelastin are modified to allysine residues.

• Neighbouring tropoelastin are joined to form desmosine cross-link in which four chains of tropoelastin are linked together.

• PROPERTIES: Elastin form an interconnected rubbery network that can impart stretchiness to the tissue that contains it.

• Structure resembles collection of rubber bands that have been knotted together with the knots being the desmosine cross-links, because of which elastin can adopt different shapes both when relaxed and when stretched.

Fibrous Protein-Elastin

Adhesion Proteins

• These proteins join and organize ECM and also link cells to ECM.

• Fibronectin is the principal adhesive protein in connective tissues while laminin in epithelial tissues.

• Both contain three different binding domains or regions that link them to cells and other components of ECM including proteoglycans and collagen.

Summary• Matrix of macromolecules in the extracellular space- ECM.• ECM is secreted by cells that live within the tissue. • Physical nature of ECM also varies from tissue to tissue. • Three categories of extracellular macromolecules make up ECM:• PROTEOGLYCANS: Aggregates of protein and glycoaminoglycans (GAGs)-

Resilence of joints and slippery consistency of mucous.• FIBROUS PROTEINS: Collagen and Elastin which are the major components

of connective tissues-provide strength and integrity.• ADHESIVE PROTEINS: Fibronectin and laminin are glycoproteins- join and

organize ECM.