Extracellular matrix

What is the extracellular matrix (ECM)?

An organized network of extracellular materials secreted by surrounding cells that provides structural and biochemical support to cells.

Name the main components of the ECM.

Structural proteins (collagen, elastin), specialized adhesion proteins (fibronectin, laminin, integrin), and proteoglycans.

What are the functions of the ECM?

Provides shape and support, enables cell signaling, offers strength and resistance, supports nutrient/waste transport, and anchors cells.

In what physical states can ECM exist?

Solid (bone), semi-solid (cartilage), and liquid (blood, lymph).

What are structural proteins of the ECM?

Collagen and elastin.

What is collagen?

A family of fibrous glycoproteins with high tensile strength, forming triple helices of three polypeptide chains.

Which types of collagen are most abundant?

Types I, II, and III.

Where is type I collagen found?

Skin, tendon, bone, ligaments, dentin, and interstitial tissues.

Where is type II collagen found?

Cartilage and vitreous humor.

Where is type III collagen found?

Skin, muscle, and blood vessels.

What is the main structural feature of collagen?

A trimer of three α-chains wound into a rod-like triple helix.

What amino acids are abundant in collagen?

Glycine and proline (many hydroxylated to stabilize the helix).

Which vitamin is essential for collagen hydroxylation?

Vitamin C (ascorbic acid).

What disease results from vitamin C deficiency?

Scurvy, characterized by poor wound healing, tooth loss, and fragile connective tissue.

What causes Ehlers-Danlos syndrome?

Mutations in type I or III collagen genes causing hyperflexible joints and stretchy skin.

What causes osteogenesis imperfecta?

Type I collagen gene mutations leading to brittle bones.

What causes Alport syndrome?

Type IV collagen mutations affecting the glomerular basement membrane in kidneys.

What is elastin?

A hydrophobic protein that provides elasticity and recoil to tissues like skin, lungs, and arteries.

What amino acids are abundant in elastin?

Ala, Val, Leu, and Gly.

What are desmosine and isodesmosine?

Lysine derivatives that cross-link elastin fibers for strength and elasticity.

What is fibrillin?

A glycoprotein that forms microfibrils and provides scaffolding for elastin deposition.

What disease is caused by fibrillin mutations?

Marfan’s syndrome.

What are adhesion proteins?

Fibronectin, laminin, and integrin.

What is fibronectin?

An adhesive glycoprotein that binds collagen, proteoglycans, and cell receptors to promote adhesion and signaling.

What sequence in fibronectin binds to integrins?

RGD (Arg-Gly-Asp) sequence.

Where is tissue fibronectin found?

In connective tissue and healing wounds.

Where is plasma fibronectin produced?

In the liver; it circulates in blood and participates in clot formation.

What enzyme links fibronectin to fibrin in blood clots?

Transglutaminase.

What is laminin?

A cross-shaped glycoprotein of α, β, and γ chains found in the basal lamina.

What are laminin’s functions?

Anchors cells, organizes basal lamina, supports migration, growth, and survival.

Defective laminin causes which diseases?

Muscular dystrophy, junctional epidermolysis bullosa, nephrotic syndrome.

What are integrins?

Transmembrane receptors connecting ECM to cytoskeleton; mediate adhesion and signal transduction.

How are integrins activated?

By inside-out signaling that increases ligand affinity.

What happens when integrin function is lost?

Impaired adhesion, possible metastasis in cancer.

What are proteoglycans?

Protein–polysaccharide complexes with GAG chains that form hydrated gels in the ECM.

What are GAGs?

Glycosaminoglycans—repeating disaccharide chains that attract cations and water, forming gels.

Name examples of GAGs.

Hyaluronic acid, chondroitin sulfate, dermatan sulfate, keratan sulfate, heparin.

What is the function of proteoglycans?

Provide cushioning, resist compression, and retain water in tissues like cartilage and skin.

What are heparan sulfate proteoglycans (HSPGs)?

Co-receptors at cell surfaces that regulate growth, angiogenesis, and act as viral receptors.

What is the basement membrane (basal lamina)?

A thin ECM sheet containing collagen IV, laminin, and proteoglycans that underlies epithelial and endothelial cells.

Functions of the basement membrane?

Provides mechanical support, signals survival, guides migration, separates tissues, and acts as a permeability barrier.

What ECM components are abundant in bone?

Collagen and proteoglycans impregnated with calcium phosphate.

What ECM defect causes decreased skin elasticity with aging?

Excess collagen cross-linking and elastin degradation.