1.13: Extracellular Matrix 1

Question 1

What is the defining feature of connective tissue?

Answer 1

Extracellular Matrix

Question 2

What are the roles of connective tissues?

Answer 2

1) bind structures together
2) form a framework and support for organs and body as a whole
3) store fat
4) transport substances
5) protect against disease
6) help repair tissue damage

Question 3

How are connective tissues characterized?

Answer 3

an abundance of intracellular matrix with relatively few cells

Question 4

What is the extracellular matrix?

Answer 4

non-cellular components present within all tissues and organs

Question 5

What is the ECM composed of?

Answer 5

water, proteins and polysaccharides

-some cells, non-living ground substance, collagen fibers, elastic fibers, reticular fibers

Question 6

What’s the ECM role? (scaffolding and biochemically)

Answer 6

1) Physical scaffolding for cellular constituents
2) Initiates crucial biochemical and biochemical cues required for tissue morphogenesis, differentiation and homeostasis.

Question 7

What are the two components of the extracellular matrix/extracellular macromolecules?

Answer 7

1) glycosaminoglycans

2) proteoglycans

Question 8

What two things make up the ECM: Name two main classes of extracellular macromolecules and one more?

Answer 8

1) Proteoglycans: Glycosaminoglycans –> covalently linked to protein
2) Fibrous protein: fibronectin, laminin, elastin, collagen (FLEC)

Question 9

Describe the composition of GAG?

Answer 9

-long unbranched chain polymers of repeated disaccharides containing an amino sugar.

Question 10

What are the four major classes of GAG?

Answer 10

1) Hyaluronan
2) Chondroitin sulfate: (Dermatan–> 5th GAG class that’s associated with the chondroitin family)
3) Heparan sulfate
4) Keratan sulfate
(if you look at the structures, many of these molecules are sulfated)

Question 11

Composition & Function of Hyaluronan/hyaluronic acid:

Answer 11

a disaccharide with glucuronic acid attached and is an extremely long and rigid GAG is composed of several thousand units of sugar.

• NO PROTEIN CORE
• Proteoglycans (GAGs+ core protein) link to hyoluronic acid via Link Protein = proteoglycan aggregates

Function: Cell migration in: embryogenesis, morphogenesis, wound healing.

Question 12

Function of chondroitin sulfate?

Answer 12

Formation of bone, cartilage, cornea

Question 13

Keratan sulfate?

Answer 13

Transparency of cornea

Question 14

Heparan sulfate?

Answer 14

Component of skin fibroblasts and aortic wall, commonly found on cell surfaces

Question 15

What are proteoglycans?

Answer 15

another class of macromolecules of the cell surface or ECM where one or more GAG chains are joined covalently to a membrane or secreted protein.

-the carbhydrate portion forms the greater fraction by mass

Question 16

What are proteoglycan aggregates?

Answer 16

when proteoglycans are attached to hyaluronic acid via a Linker protein. ( PROTEOGLYCAN (GAGS) + LINKER PROTEIN + HYALURONIC ACID)

Question 17

How are proteoglycans classified?

Answer 17

classified according to their core proteins, localization and GAG composition.

Question 18

What are the three proteoglycan families?

Answer 18

1) Small leucine-rich proteoglycans (SLRPS)
2) Modular proteoglycans (family of proteins where they all share similar domains)
3) Cell-surface proteoglycans (These proteoglycans are embedded into membrane)

Question 19

What are the properties of proteoglycans? (3)

Answer 19

1) Highly hydrophilic and accordingly adopt extended conformations
2) Conformations essential for hydrogel formation
3) enables matrices that are formed by these molecules to withstand high compressive forces.

Question 20

Pros of negatively charged proteoglycans?

Answer 20

They attract ions and water, thus forming a gel.

Question 21

Role of the poylsaccharide gel in proteoglycans?

Answer 21

• Resists compressive forces on the matrix

- Permit rapid diffusion of nutrients, metabolites and hormones between the blood and the tissue cells.

Question 22

Role of collagen fibers in ECM?
Role of Elastin fibers in ECM?
Role of protein fibers in ECM?

Answer 22

• Help strengthen and organize the ECM
• Rubberlike elastin fibers give it resilience.
• Matrix proteins help cells attach in the appropriate locations

Question 23

Can proteoglycans form proteoglycan aggregates?

Answer 23

Yes, some can.

Question 24

What is the composition of Hyaluronate as a biological shock absorber?

Answer 24

• composed of repeating units of D-glucuronate and N-acetyl-D-glucosamine linked through 1-3Beta glycosidic bonds.
• This repeating disaccharides are linked by 1-4Beta glycosidic bonds
• Beta configuration gives polymer a stretched conformation, made more linear because of electrostatic repulsion of negative charge.
• Because of the negative charge, the strand is now heavily solvated with water; therefore, giving remarkable viscosity and tensil properties.

Question 25

Role of Syndecan-1? | What does Syndecan bind?

Answer 25

Proteoglycan can be anchored in the membrane (Syndecan-1): plays important role in inflammation/wound healing) Syndecan-1 binds CHEMOKINES. - When epithelia are damaged, these complexes are released and diffuse away forming a chemotactic gradient that attracts neutrophils to the site. -Syndecan-1 also plays important role in cell binding and cell signaling.

Question 26

Synthesis of proteoglycans in the cell? (Anabolism)

Answer 26

- The protein backbone is formed at the rough endoplasmic reticulum - Protein chain is then transferred to golgi and sugars are added forming GAGs - GAGs leave golgi and become part of the cell membrane.

Question 27

Breaking down of proteoglycans in the cell? (Catabolism) | - What are the requirements for these breakdowns?

Answer 27

- Proteogylcans are taken into the cell by endocytosis and degraded by lysosomes - Amino acids and sugars in proteoglycans are recycled when ever possible - Requires 3 exoglycosidases, 4 sulfatases, and 1 acetyl transferase with stepwise removal of monosaccharides.

Question 28

Where does normal catabolism occur? (proteoglycans)

Answer 28

seen in remodeling of cartilage and bone

Question 29

where does abnormal catabolism occurs? (proteoglycans)

Answer 29

seen in arthritis and tumor invasions

Question 30

Where do most breakdowns occur? | -What do inhibitors here do?

Answer 30

via lysosomal pathways. | - inhibitors reduce break down of linear proteins by extracellular proteases.

Question 31

What are GAG defects? | A Lysosomal storage disease.

Answer 31

- normally due to an enzyme deficiency and so proteoglycans get accumulated. - Chondroitin sulfate and hyaluronate do no accumulate because they can be catalyzed via a different pathway... so it's usually with heparan or dermatan sulfate. - due to autosomal recessive or X linked - there are severe and mild forms of the disease - Not apparent at birth ex: Hunter disease -