BMI09 - ECM and Connective Tissue

What is connective tissue?

Connective tissue is tissue that supports, connects, or separates different types of tissues and organs.

What are the main components of connective tissue?

Connective tissue is composed of extracellular matrix (ECM), protein fibers, and cells.

What components make up the ground substance of connective tissue ECM?

The ground substance of connective tissue ECM contains glycoproteins such as laminin and fibronectin, glycosaminoglycans (GAGs), and proteoglycans.

What are the three major types of protein fibers found in connective tissue?

The three major types of protein fibers in connective tissue are collagen fibers, reticular fibers, and elastic fibers.

What is the structure of collagen fibers in connective tissue?

Collagen fibers are linear fibers that provide tensile strength and firmness.

What is the structure of reticular fibers in connective tissue?

Reticular fibers are mesh-like fibers that form supportive networks.

What forms elastic fibers in connective tissue?

Elastic fibers are formed by microfibrils composed of elastin and fibrillin.

What are fixed resident cells in connective tissue?

Fixed resident cells are cells such as fibroblasts, chondrocytes, adipocytes, osteoblasts, and odontoblasts that secrete extracellular matrix.

What are examples of free cells in connective tissue?

Examples of free cells in connective tissue include macrophages and lymphocytes.

What is the extracellular matrix (ECM)?

The extracellular matrix is a complex network of macromolecules secreted by local cells.

What are the functions of the extracellular matrix?

The extracellular matrix functions in structural support, cell migration, cell adhesion, and signal relay.

What are the major fibrous proteins of the ECM?

The major fibrous proteins of the ECM are collagen, elastin, and fibrillin.

What are the general properties of collagen, elastin, and fibrillin?

Collagen, elastin, and fibrillin are insoluble, stable proteins with long biological half-lives and unique structures that give them specific mechanical properties.

What mechanical property does collagen provide?

Collagen provides tensile strength and firmness.

What mechanical property does elastin provide?

Elastin provides contractility and elasticity.

What percentage of total body protein is collagen?

Collagen accounts for approximately 25–30% of the total protein content of the body.

What is the role of collagen in the body?

Collagen is the primary component of the extracellular matrix.

How many types of collagen exist?

There are 28 collagen types.

What are the major groups of collagen?

The major groups of collagen are fibril-forming collagens, network-forming collagens, and fibril-associated collagens.

Which collagen group makes up more than 90% of collagen?

Fibril-forming collagens make up more than 90% of collagen.

Which collagen types are fibril-forming collagens?

Fibril-forming collagens include types I, II, III, V, and XI.

What is the structure of fibril-forming collagens?

Fibril-forming collagens form well-organized, rope-like fibrils.

What characteristic appearance do fibril-forming collagens show under electron microscopy?

Fibril-forming collagens show a banded pattern under electron microscopy due to staggered packing.

What is the function of fibril-forming collagens?

Fibril-forming collagens provide tensile strength for tendons, ligaments, and skin.

Which collagen types are network-forming collagens?

Network-forming collagens include types IV and VIII.

What structural feature distinguishes network-forming collagens?

Network-forming collagens contain triple-helical fragments interrupted by non-helical structures.

What structure do network-forming collagens form?

Network-forming collagens form three-dimensional meshes or sheets.

Where are network-forming collagens commonly found?

Network-forming collagens are part of basement membranes, where they provide mechanical support for cells.

Which collagen types are fibril-associated collagens?

Fibril-associated collagens include types IX and XII.

What is the function of fibril-associated collagens?

Fibril-associated collagens link collagen fibrils to each other or to other ECM components.

How many genes encode collagen proteins?

Forty-six genes encode collagen proteins.

What determines the function of collagen molecules?

The organization of collagen proteins determines their function.

What is the amino acid sequence pattern of collagen alpha chains?

Collagen alpha chains contain repeating polytripeptide sequences of Gly-X-Y.

Which amino acid occupies every third position in collagen alpha chains?

Glycine occupies every third position in collagen alpha chains.

What amino acid is commonly found in the X position of collagen?

Proline is commonly found in the X position of collagen.

What is the role of proline in collagen structure?

Proline forms kinks that contribute to the helical structure of collagen.

What amino acids are commonly found in the Y position of collagen?

Hydroxyproline and hydroxylysine are commonly found in the Y position of collagen.

How is collagen organized structurally?

Three polypeptide alpha chains, which may be identical or different, form a triple-helical structure stabilized by interchain hydrogen bonds.

What is the structure of an individual collagen alpha chain?

Each collagen alpha chain is a left-handed helix with three residues per turn.

What is tropocollagen?

Tropocollagen is the rope-like structure formed when three collagen alpha chains twist together in a right-handed helical configuration.

What are the steps of collagen biosynthesis?

The steps of collagen biosynthesis are pro-alpha chain formation, hydroxylation, glycosylation, assembly, secretion, extracellular cleavage, collagen fibril formation, and cross-link formation.

Which steps occur in the ER?

1. Pro alpha-chain formation

2. Hydroxylation

Which steps occur in the cytosol?

3. Glycosylation

4. Assembly

5. Secretion

Which steps occur in the ECM?

6. Extracellular cleavage

7. Collagen fibril formation

8. Cross-link formation

Where does pro-alpha chain formation occur during collagen biosynthesis?

Pro-alpha chain formation occurs in the rough endoplasmic reticulum.

How are collagen alpha chains initially synthesized?

Collagen alpha chains are synthesized as pre-pro-alpha chains containing an N-terminal signal sequence for secretion.

What happens to the signal sequence during collagen synthesis?

The signal sequence is cleaved in the ER lumen to form the pro-alpha chain.

Which amino acids are hydroxylated during collagen synthesis?

Proline and lysine residues are hydroxylated during collagen synthesis.

Which proline residues are specifically hydroxylated in collagen?

Hydroxylation is highly specific for prolines attached to the amino group of glycine.

What cofactor do collagen hydroxylases require?

Collagen hydroxylases are Fe2+-dependent enzymes.

Why is hydroxylation important in collagen synthesis?

Hydroxylation is required for the formation of interchain hydrogen bonds that stabilize the triple helix structure.

What type of glycosylation occurs on hydroxylysine residues in collagen?

O-linked glycosylation occurs on hydroxylysine residues.

Which sugars are added during O-linked glycosylation of collagen?

Glucose or glucosyl-galactose residues are added during O-linked glycosylation.

Which enzymes add sugars during collagen glycosylation?

Glucosyltransferases and galactosyltransferases add sugars during collagen glycosylation.

What type of glycosylation occurs on arginine residues in nonfibrillar collagens?

N-linked glycosylation occurs on arginine residues in nonfibrillar collagens.

What is procollagen?

Procollagen is the collagen precursor composed of a central helical region flanked by globular N-terminal and C-terminal propeptides.

How are collagen chains aligned into a triple helix during assembly?

Intra- and interchain disulfide bonds formed at the C-terminal propeptides help align the chains into a triple helix.

How is procollagen secreted from the cell?

Procollagen is secreted by exocytosis.

What happens during extracellular cleavage of collagen?

Specific proteinases cleave the N-terminal and C-terminal propeptides of procollagen to form tropocollagen.

How do tropocollagen molecules organize into fibrils?

Tropocollagen molecules spontaneously organize into ordered parallel arrays with staggered patterns.

How much does each tropocollagen molecule overlap its neighboring molecule in collagen fibrils?

Each tropocollagen molecule overlaps its neighboring molecule by approximately three-fourths of its length.

What enzyme catalyzes collagen cross-link formation?

Lysyl oxidase catalyzes collagen cross-link formation.

What cofactor is required for lysyl oxidase activity?

Lysyl oxidase is copper-dependent.

What reaction does lysyl oxidase perform in collagen maturation?

Lysyl oxidase deaminates lysine and hydroxylysine residues to form reactive aldehydes called allysine and hydroxyallysine.

How are covalent cross-links formed in collagen?

Reactive aldehydes condense with lysine and hydroxylysine residues to form covalent cross-links.

What are intramolecular collagen cross-links?

Intramolecular cross-links occur within the alpha chains of tropocollagen.

What are intermolecular collagen cross-links?

Intermolecular cross-links occur between tropocollagen molecules.

What is mature collagen?

Mature collagen consists of cross-linked collagen fibrils.

What are collagen cross-bridges?

Cross-bridges are cross-links between the N-terminus of one tropocollagen molecule and the C-terminus of an adjacent tropocollagen molecule.

How many collagen cross-links are present in young, rapidly growing tissues?

Young, rapidly growing tissues contain a small number of collagen cross-links.

Why do young tissues have fewer collagen cross-links?

Young tissues have fewer collagen cross-links because they require high turnover for growth and remodeling.

How does collagen cross-linking change with age?

Collagen becomes more highly cross-linked with age.

What is the biological half-life of normal collagen?

Normal collagen is highly stable and has a half-life of years.

How is collagen degraded?

Collagen is degraded by collagenases belonging to the matrix metalloproteinase (MMP) family.

What are pyridinoline and deoxypyridinoline?

Pyridinoline and deoxypyridinoline are collagen cross-bridges measured in blood and urine as markers of bone degradation.

What is the composition and arrangement of collagen in the sclera?

The sclera contains large bundles of mostly type I collagen arranged in an irregular, interwoven pattern.

What properties does scleral collagen provide?

Scleral collagen provides a white, tough, opaque shell for the eye.

What is the collagen composition of the conjunctiva?

The conjunctiva contains a complex multilayered collagen network composed mainly of type IV and type III collagen.

What property does the conjunctival collagen network provide?

The loose collagen network of the conjunctiva accommodates eyelid movement.

What type of collagen predominates in the cornea?

Type I collagen predominates in the cornea.

Why is corneal collagen precisely organized?

Precise organization of corneal collagen reduces light scattering, provides transparency, withstands intraocular pressure, and maintains anterior eye curvature.

What type of collagen is found in the retina?

The retina mainly contains type IV collagen in vascular basement membranes and lacks prominent fibrillar bundles.

What are fibroses?

Fibroses are disorders involving increased collagen synthesis stimulated by tissue damage.

What conditions are examples of fibrosis?

Hepatic cirrhosis and pulmonary fibrosis are examples of fibrosis.

What can cause decreased collagen synthesis?

Decreased collagen synthesis can result from genetic disorders or acquired disorders such as vitamin C deficiency and copper deficiency.

What are collagenopathies?

Collagenopathies are disorders involving abnormalities in collagen synthesis or structure.

What causes genetic collagen disorders?

Genetic collagen disorders result from defects in any step of collagen biosynthesis and involve more than 1000 known mutations.

What is Ehlers-Danlos syndrome?

Ehlers-Danlos syndrome is an autosomal dominant disorder caused by defects in collagen metabolism, including deficient processing enzymes or mutations in amino acid sequences.

What collagen type is affected in the classic form of Ehlers-Danlos syndrome?

The classic form of Ehlers-Danlos syndrome involves type V collagen defects.

What are the symptoms of classic Ehlers-Danlos syndrome?

Classic Ehlers-Danlos syndrome causes skin fragility, joint hypermobility, thin hyperextensible skin, and slow wound healing.

What collagen type is affected in the vascular form of Ehlers-Danlos syndrome?

The vascular form of Ehlers-Danlos syndrome involves type III collagen defects.

What are the symptoms of vascular Ehlers-Danlos syndrome?

Vascular Ehlers-Danlos syndrome causes bruising, arterial rupture, and mitral valve prolapse.

What is brittle cornea syndrome?

Brittle cornea syndrome is a disorder characterized by thin corneas with keratoconus.

What is scurvy?

Scurvy is a disease caused by vitamin C (ascorbic acid) deficiency.

How does vitamin C deficiency affect collagen synthesis?

Vitamin C deficiency prevents formation of interchain hydrogen bonds, leading to unstable loose helices, intracellular degradation, and loss of collagen in the ECM.

How long does vitamin C deprivation usually take before symptoms of scurvy develop?

Symptoms of scurvy usually develop after more than three months of vitamin C deprivation.

What are the symptoms of scurvy?

Symptoms of scurvy include weakness, fatigue, petechiae due to vascular fragility, and poor wound healing.

What ocular hemorrhages can occur in untreated scurvy?

Untreated scurvy can cause hemorrhage of the eyelids, conjunctiva, orbit, iris, and retina.

What tissues commonly contain elastic fibers?

Elastic fibers are commonly found in lungs, large arteries, ligaments, and skin.

What forms elastic fibers in the ECM?

Elastic fibers are formed by elastin deposited on a fibrillin scaffold.