6. Extracellular Matrix Flashcards

1
Q

what roles does the Extracellular matrix play?

what things require an appropriate ECM?

A

organization: control of cell behavior by binding of growth factors and interaction with cell surface receptors
protection: milieu for inflammatory response, retains water, buffering against extracellular change
mechanical: tensile and compressive strength, elasticity

cell differentiation, migration, proliferation all require ECM

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2
Q

what forms does the ECM take?

what are the major proteins of these structures?

A

consists of
basil laminae:
-collagen type 4, proteoglycans, glycoproteins

fibrils:
-collagen 1, 2, 3, fibroncectin, and elastin

amorphous matrix (ground substance):

  • hyaluronic acid
  • proteoglycans, and glycoproteins
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3
Q

where is basal lamina found?

especially in what cells?

A

underlies all epithelia including endothelium in blood vessels;
the epithelial cells rest on the basal lamina

especially in the muscle, epithelium , schwa cells in peripheral nerve, and kidney glomerulus where it helps keep protein from filtering through

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4
Q

what are some of the major proteins in the network of basal laminae proteins?

what are they linked by?

A

-type 4 collagen fibers, integrin, laminin, and heparan sulfate proteoglycans which are all linked together by smaller protein nidogen

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5
Q

what is the clinical importance of basal lamina?

A
  • regeneration of epithelium (e.g. after burns)
  • neccessary for regeneration of muscle fibers and peripheral axons
  • inhibits growth of tumors
  • can have autoimmune diseases bc of attachment structures
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6
Q

what is the amorphous matrix?
how does it stain?
functions?

A

-stains poorly
-consists of hyaluronic acid
-sulfated proteoglycans
-adhesive glycoproteins
collagens type I and/or III
serum proteins and growth factors

functions:

1) suspend and support connective tissue cells
2) permits diffusion of gas and solutes
3) inhibits invasion of bacteria

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7
Q

what are proteoglycans?

what are glycosaminoglycans?

A

glycosaminoglycans: GAG
- glycos: long chains of repeating disacharides
- amino: attached to protein core
- glycans: protein core is sulfated—> highly negative charge

proteoglycans are proteins with covalently attached glycosaminoglycan side chains (like a bottle brush)

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8
Q

what is the function of GAGs and proteoglycans in the ground substance?

A
  1. hydration of the ECM …especially aggrecan in cartilage and hyaluronic acid in embryos
  2. Shock absorption (negative charges repel with pressure applied)
  3. filtration (think kidney glomerular basement)
  4. link ECM to cytoskeleton
  5. lubrication
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9
Q

the cartilage proteoglycan- aggrecan is important bc?

A

this proteoglycan acts as shock absorber in the amorphous ground substance
-aggrecan is pretty big (size of 0.3 micrometers) and has hyaluronic acid and GAGs including chondroitin sulfate and derma tan sulfate

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10
Q

what are important proteoglycans in the basal lamina?

what are they important for?

A

perlecan and agrin

  • agrin important as major heparin sulfate proteoglycan in the glomerular basement membrane
  • sulfate groups charge keep proteins from leaking into the urine
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11
Q

why is syndecan important?

A

it is an integral membrane proteoglycan that links actin cytoskeleton to ECM molecules

-hydrophobic tail allows it to integrate into the lipid bilayer

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12
Q

what is fibronectin? what are the 2 types?

A

adhesive glycoproteins
-necessary for cells to attach and spread on a collagen substrate in culture

  • its in the amorphous matrix
    1) cellular: insoluble, occursin fibrils laid down by cells
    2) plasma: very soluble, binds to fibrin and involved in blood clotting
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13
Q

what are integrins and why are they important?

A

they are receptors for firbonectin and other ECM proteins. they link the ECM to the cytoskeleton

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14
Q

what is laminin?

how does it bind?

A

large adhesive glycoprotein of basal lamina

  • essential for epithelial cell function and polarity
  • ** essential for epithelial cell differentiation

-binds epithelial cells to basal lamina via the integrins

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15
Q

what are the fibers of connective tissue? describe them

A

collagen: 1-20 um in diameter. made up of microfibrils

elastic: smaller in diameter than collagen, much longer, branched
- veerrry stretchy ( 5 x more elastic than rubber bands)
- consist of elastin protein
- form plates with walls of some arteries

histology: elastic fibers are thin and branched while collagen fibers are thick and ropy

reticular fibers: composed of type III collagen, small diameter and short. inelastic, but flexible.
-form stroma (supporting structure) of many soft tissues such as liver and spleen

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16
Q

describe marfans syndrome?

A

autosomal dominant (1/10,000 to 20,000)

mutations in FIBRILLIN

  • pts typically tall with long limbs and long thin fingers (arachnodactyly- spider like digits)
  • defects of heart valves and aorta most common—> aortic dissection is common and ca nbe fatal

-s/s may be result of excess transforming growth factor beta which binds to fibrillin

17
Q

what is the most abundant protein in animals? and what is the structure?

A

collagen
25% of the total

  • triple helical sequence of glycine-proline-x(aa)
  • has tensile strength greater than steel.
18
Q

know type 1-4 of collagen fibers. list them and describe them

A

Types 1-3 are fibrillar:

  • type I made by cells of loose and dense conn. tissue
  • 90% of the collagen
  • nearly all triple helical
  • banded- which you can see
  • type II made by chondroblasts in cartilage
  • type II is reticular fibers in skin, blood vessels, and internal organs

Type 4 is in basal lamina (schwa an cells, fat, muscle, endothelia, etc)

19
Q

how is collagen made?

A
  1. synthesis of pro-alpha chain
  2. hydroxylation of prolines and lysines (propyl hydroxylase….scurvy)
  3. glycosylation of selected hydroxylysines
  4. self assembly and secretions
20
Q

how do collagen molecules cross link?

A

requires oxidation of lysine and hydroxylysines extracellularly. also requires hydroxyproline
-but covalently bonds to form cross link

21
Q

what regulates the diameter of collagen type 1 fibrils?

A

types 5 and 6

22
Q

why is collagen type 9 important?

A

type 2 collagen fibrils in cartilage bind type 9 collagen

23
Q

collagen fibrils are made by

A

fibroblasts

24
Q

diseases involving collagen:

A
  1. osteogensis imperfecta- mutation in gene coding for colalgen type I
  2. ehlers-danlos syndrome:
    - decreased collagen III synthesis: aortic rupture, thick skin
    - faulty lysine hydroxylation: can’t cross-link collagen
    * hyperextensible skin
  3. scleroderma: excessive fibrosis caused by too much collagen production.
    epidermis is thin and atrophied.
    Dermis adheres to deepr connective tissue. “stone skin disease”