10.2 Extracellular Matrix

Question 1

What is the extracellular matrix (ECM)?

Answer 1

not a cell or part of the cell (outside the cell) made up of material known as ground substance along with a variety of types of imbedded protein fibers.

-ECM is made up by cells and plays a significant role in determining the behavior of cells in it.

Question 2

What is connective tissue?

Answer 2

Connective tissue forms most of the extracellular matrix material in our bodies. It has a variety of roles, including the formation of conduits for nerves and blood cells.

It also provides supporting material for cellular organs such s the liver and kidney and

It performs a variety of mechanical roles in our bodies, including the formation of:

1) the skeletal systems
2) Tendons and ligaments

Question 3

What is a basal lamina?

Answer 3

layer of extracellular matrix material that is found at the base of all epithelial and endothelial cells. Sometimes it’s called basement membrane. This fibrous sheet of material separates an epithelial tissue from the underlying connective tissue.

Question 4

Which protein is found in abundance in the connective tissue?

Answer 4

Collagen Type 1

Question 5

What proteins/structures can you find in connective tissue?

Answer 5

Collagen Type 1

Blood vessels

Nuclei fibroblasts

Question 6

What is the role of the fibroblasts in connective tissue?

Answer 6

fibroblasts are the cells that are responsible for making the connective tissue. They do so by producing collagen fibers.

Fibroblast or spindly or pointy in appearance

Question 7

How do fibroblasts and other cells navigate through the extracellular matrix?

Answer 7

To navigate through the matrix the secrete proteases which digest the fibers and other components of the extracellular matrix

Question 8

What are chondroblasts?

Answer 8

cells that make cartilage and when they become imbedded in the cartilage material they’re called chondrocytes

Question 9

What are osteoblasts?

Answer 9

cells that form bone. When osteoblast become embedded in bone material they’re called osteocytes

Question 10

What three major components comprise ground substance?

Which makes up most of the ground substance?

Answer 10

1) Glycosaminoglycans or (GAGs)
2) Glycoproteins
3) Proteoglycans

GAGs make up most of the ground substance

Question 11

What is the structure of GAGs (glycosaminoglycans)? What other major characteristic stands out about GAGs?

Answer 11

a long chain of sulfated polysaccharides, which consist of a disaccharide of some type, strung together in a long row.

The types of sugar disaccharides that are used to form these chains determine what type of a glycosaminoglycan it is.

CHARACTERISTIC:

They have many negative charges. These negative charges attract sodium ions, which is positively charged, and in turn sodium will attract water.

Question 12

What are examples of glycosaminoglycans (GAGs)?

Answer 12

1) Hyaluronan
2) chondroitin sulfate (found in cartilage)
3) dermatan sulfate (found in skin)
4) Keratan sulfate (found in eptihelial)

Question 13

How do glycosaminoglycans (GAGs) form gel like material in the extracellular matrix? Why is this significant?

Answer 13

GAGs have many negative charges, which attracts sodium. Sodium invites water to the party. This causes GAGs to form a gel-like material when they’re swollen with water.

The gel material gives the extracellular matrix its physical properties. Resists compression factors

Question 14

What is hyaluronic acid?

Answer 14

the simplest GAGs. it is a linear chain of linked disaccharides, other gags are not present as a simple linear chain (instead they form more complex structures)

Question 15

What are proteoglycans and how are they formed?

Answer 15

Type of glycosaminoglycans.

It is formed by linking a simply glycosaminoglycan to a protein core. There are many diff proteins that can form the core and a variety of glycosaminoglycan side chains can be linked to the core, and this gives the extracellular matrix its molecular complexity.

Question 16

How are glycosaminoglycan side chains in proteogylcans linked to the core protein?

Answer 16

via a special tetra-saccharide (it has four sugar moieties), which forms an adaptor link between the glycosaminoglycan side chain and the core protein.

Makes proteoglycans diverse. in configurations.

Question 17

What are proteoglycan aggegates? How are they formed?

Answer 17

the most complex GAG. They are proteoglycans which are then linked back to a central hyaluronic acid molecule.

FORMED:
They are formed by linking core proteins to a GAG core with linker proteins. For example protegylcans are linked to a central hyaluronic acid molecule. They are linked by linker proteins. They are very large molecules! about 15 microns long

(WILL BE ON EXAM FOR SHIZZLE)

Question 18

What are the functions of GAGs?

Answer 18

GAGs perform variable functions.

1) Fill up spaces that are not occupied by other cells or fibers. This is a function that’s obvs when you consider their size.
2) Attract salt ions and water and maintain Na+/H2O balance of tissues
3) Regulate proteins found w/in extracellular matrix. ( EX:
1) immobilize proteins and limit their range of activity or protect them from degradation aka prolonging their activity)
2) Inactivate protein/signaling factors by binding to them until they’re worked on by other cells in the matrix
3) Concentrate proteins in a limited area

Question 19

What types of issues can occur if GAGs don’t regulate Na+/H2O balance in tissues?

Answer 19

deregulation of this balance can cause metabolic abnormalities, tissue edema, which is filling of tissues with free water.

Question 20

What bodily process shows the functions of glycosaminoglycans (GAGs)

Answer 20

Inflammation in response to local infection.

Cells in the region around an infection site release signaling molecules like inflammatory cytokines, and other cells of the immune system need to hone in on these signals in a directional manner, and so the signaling has to be present at a high concentration in the area of the infection and then the concentration has to dwindle as you move away from the infection site. If the inflammatory cytokines were able to move freely and rapidly throughout the entire body, the information contained in this concentration gradient would be spread out and lost.

Question 21

How do glycosaminoglycans form barriers that influence the movement of fluid across tissue? What is a bodily process that shows this?

Answer 21

b/c glycosaminoglycans interact so strongly with water molecules (the eff w/water)

Ex: the filtration apparatus of the kidney.

The primary filtration site in the kidney is a structure called the glomerulous. The core glomerulous is a know of permeable capillary tubes and surrounding these capillaries is a unique cell type called a podocyte.(which wraps capillaries with finger like protrusions)

Podocytes are very leaky. but the basement of these are filled with perlecan, which is a GAG

In healthy individuals, fluid which contains metabolic byproducts will leak through this filter, but the filter excludes things like red blood cells and even larger proteins. If you get defects in this barrier then proteins and even bllood cells will begin to show up in the urine.

Question 22

What are glycoproteins

Answer 22

(fibronectin and laminin) are large proteins w/many adhesion sites for fibers, GAGs, and cell surface receptors. Their function is to link all of these components together physically.

Glycoproteins have small amounts of polysaccharides. these polysaccharides are much smaller than the long chains which form glycosaminoglycans

Question 23

What is the structure of laminin?

Answer 23

A trimer of three subunits known as alpha, beta, and gamma chains. The trimer forms an extended coiled coil domain and is characterized by numerous globular domains that serve as binding sites for the ECCM

Question 24

Where is laminin most commonly found?

Answer 24

epithelial cells. It underlies epithelial cell monolayers. it is abundant in and helps form basal lamina. Laminin is also recognized by other cell integrins

Question 25

What is the role of laminin?

Answer 25

supports and promotes cell attachment and migrations

Question 26

What is the difference between laminin and fibronectin?

Answer 26

Unlike laminin, which is found in the basal lamina, fibronectin is found in all connective tissue

Question 27

What is the role of fibronectin?

Answer 27

it mediates the attachment of fibroblast to the ECM components.

Fibronectin deletions are embryonic lethal mutations.

Question 28

What is the structure of fibronectin?

Answer 28

fibronectin contains a number of globular domains, which form binding sites for components of the ECM and forms fibroblasts.

Binding sites are heparin binding site, self association domain, and cell binding domain.

Question 29

what does the heparin binding site on fibronectin do?

Answer 29

attaches to the glycosaminoglycans and collagen binding domain which links fibronectin to collagen fibers

Question 30

What does the self associating doamin on fibronectin do?

Answer 30

allows fibronectin to form large complexes

Question 31

what does the cell binding domain on fibronectin do?

Answer 31

contains a region which is attached by integrins, expressed on the surface of fibroblasts. this region contains a short peptide loop, w/three amino acids: arginine, glycine, and aspartate (RGD)

Question 32

What is the RGD Domain?

Answer 32

a classic cell attachment motif which is present in many other proteins that have to interact with the extracellular surface of cells (REMEMBER THIS)
Amino acids: arganine, glycine, aspartate and it’s found in the cell binding region of fibernectin.

facilitates attachment of fibroblasts to the surface

RGD will also bind to integrins on the cell surface and block ability of the cell to attach to its surface.

Question 33

What type of fibers are found in the extracelllar matrix?

Answer 33

collagen fibers and elastic fibers

Question 34

What are collagen fibers?

Answer 34

the most abundant protein in our bodies and it’s the basis of structural integrity of our tissues.

A collagen fiber is as strong as a steel cable. There are four types of collage.

1)collagen I
2) collagen type II
3) collagen type III
Collagen type IV

Ex: tendons and ligaments are essentially collagen fibers.

Question 35

What is collage I?

Answer 35

the most abundant type of collagen and it’s found in connective tissue (bone, tendons, and ligaments).

It forms thick unbranched linear filaments that are easy to see in microscope slides.

Question 36

What is collagen type II?

Answer 36

makes fine fibers which are difficult to see and they’re found in cartilage.

cartilage looks homogenous b/c the fibers are fine.

Question 37

What is collagen type III?

Answer 37

forms what are known as reticular fibers. Reticular fibers are highly branched fibers found in organs and have a large density of cells (liver, spleen and kidney)

Question 38

What is Collagen type IV

Answer 38

found in the basal lamina underlying epithelial cells.

Question 39

What are the steps involved in synthesis collagen (NEED TO KNOW)?

Answer 39

1) synthesis of protein monomerpro-alpha-collagen. This protein is soluble and it’s moved into the cell’s ER where it is modified by hydroxylation and glycosylation. This step requires vitamin C.
2) Formation of procallagen and release of procallagen by cells into the extracellular matrix (where it is still a soluble compound)
3) Enzymes found outside the cell (procollagen peptidase) cut off the ends of the molecules and the remaining insoluble core trimer becomes known as collagen monomer.

collagen monomers are not soluble and they assemble spontaneously with no other factors into collagen fibrils (subunits are then linked together in staggered arrangements making them strong. )

Question 40

Why is vitamin c important to collagen fibers?

Answer 40

because it supports synthesis of collagen fibers. Vitamin C deficiency prevents the synthesis of collagen fibers including those which are important for anchoring teeth into the jaw. Scurvy!!! tooth loss is one of the symptoms of scurvy which is caused by vitamin c deficiency

Question 41

In the synthesis of collagen fibers, the modification of pro-alpha-collagen in the ER (step 1 of synthesis) leads to what?

Answer 41

leads to the formation of a soluble trimer known as procollage. Procollagen is secreted by the cells into the extracelluler matrix where it is still a soluble compound

Question 42

What is elastin?

Answer 42

protein that forms elastic fibers which are found in the extracellular matrix. It is secreted in a process much like collagens. elastin is abundant in tissue that stretches (skin, heart, arteries)

Question 43

Structural arrangement of the extracellular matrix has influence over what?

Answer 43

1) cell behavior and their arrangement of the extracellular matrix fibers
2) cell survival
3) cell shape

Question 44

What happens when fibroblasts remodel fibronectin?

Answer 44

provide surface cues for cell adhesion and migration

aka cells can influence the orientation cues in the extracellular matrix.

Question 45

Which proteins assist with cell migration and how?

Answer 45

metalloproteases and serine proteases and they do so by degradation.

Hyaluronidase is produced by virulent pathogens to move through the ECM

inhibitors of protease activity are important potential targets for anti-tumor therapies.