ECM Flashcards

1
Q

Connective tissue has a high ratio of ___ to cells in connective tissue.

A

ECM

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2
Q

What function does the ECM play in connective tissue?

A

Structural - provides architectural framework

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3
Q

What determines the physical properties of the connective tissue?

A

Composition of the matrix

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4
Q

The ECM provides support for what?

A

Cells and cell layers

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5
Q

The ECM acts as a barrier to what?

A

Cells

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6
Q

The ECM acts as a passive-selective ___-___ between tissue compartments.

A

Molecular sieve

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7
Q

What acts as a solid phase regulator of cell attachment, growth and differentiation?

A

ECM

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8
Q

ECM modulates what process?

A

Mineralization process

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9
Q

What are the three structural components of ECM?

A

Fibers
Amorphous ground substance
Basement membrane

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10
Q

What is a filament?

A

A threadlike structure (2-20 nm dia.)

Typically a single molecule or linear chain of molecules

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11
Q

Microfibrils are an aggregate of what?

A

Filaments

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12
Q

What is the typical diameter of a microfibril?

A

45-100 nm diameter

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13
Q

What is an aggregate of microfibrils called?

A

A fibril

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14
Q

What is the diameter of a fibril?

A

200-500 nm diameter

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15
Q

What is an aggregate of fibrils called?

A

A fiber

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16
Q

How big are fibers?

A

1-20 micrometers in diameter

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17
Q

What are the two types of fibers in the ECM?

A

Collagen

Elastic

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18
Q

How big are bundles?

A

20-100 micrometers in diameter

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19
Q

What makes up ground substance?

A

A complex mixture of glycoproteins, gags and proteoglycans

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20
Q

Ground substance helps bind cells to what of connective tissues?

A

Fibers

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21
Q

Ground substance fills the space between what?

A

Cells and fibers in connective tissue

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22
Q

What is a glycoprotein?

A

A protein with one or more attached sugars

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23
Q

A GAG is a family of what?

A

Heteropolysaccharides

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24
Q

GAGs are very ___ and very ___ ___.

A

Hydrated

Negatively charged

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25
What is a proteoglycan composed of?
Protein core with many GAG chains attached
26
What glycoproteins are found in interstitial connective tissue?
``` Fibroconectins Elastin Fibrilins Tenascins Thrombospondins Microfibril-associated matrilins ```
27
What glycoproteins are found in basement membranes?
Laminins Nidogen/entactin Fibulin
28
What are the small leucine-rich proteoglycans?
``` Decorin Biglycan Fibromodulin Lumican Epiphycan ```
29
What are the modular proteoglycans involved in nonhyaluronan binding?
Prelecan Agrin Testican
30
What modular proteoglycans are involved in hyaluronan and lectin binding?
Aggrecan Versican Neurocan Brevican
31
The large majority of the extracellular matrix is synthesized and secreted locally by what?
Neighboring cells
32
What makes most connective tissue?
Fibroblasts
33
What specialized CT cell makes dentin?
Odontoblasts
34
What specialized CT cells makes enamel?
Ameloblasts
35
Enamel is considered to be what?
Epithelial
36
What is the most abundant protein in the body?
Collagen
37
Collagen is about ___% of the protein in the body by weight
30%
38
The cornea is about ___% protein.
64%
39
What type of helix is collagen?
Left-handed | It is a specialized "collagen helix", not a true alpha helix
40
What ring structure adds rigidity to collagen?
Proline
41
In mature form, collagen doesn't have what two amino acids?
Cystein | Tryptophan
42
What is tropocollagen
3 helical strands of collagen wrapping around each other
43
How do tropocollagen fibrils arrange themselves?
In a staggered array of parallel bundles
44
What causes striations in collagen?
Alignment of every 4th molecule
45
What forms crosslinks in collagen?
Lysinonoreleucine
46
What enzyme does the production of lysinonorleucine require?
Lysyl amino oxidase
47
Lysyl amino oxidase requires which cofactor?
Vitamin B6 (pyridoxine)
48
What does each collagen molecule consist of?
Three alpha-chains
49
The collagen family has how many different alpha-chains?
34
50
Fibrillar collagens form ___ fibers with ___ strength.
Long | Tensile
51
Non-fibrillar collagens can partially organize into how many groups?
4
52
What are the 4 types of non-fibrillar collagens?
Basement membrane collagens Fibril-associated collagen with interrupted triple helix Multiplexins Microfibrillar collagen
53
Which type of non-fibrillar collagen is the network forming collagen?
Basement membrane collagen
54
Which number types are the fibril-forming collagens?
I, II, III, V, XI
55
Fibrils can assemble into what?
Fibers
56
Fibers can assemble into what?
Bundles (ex. tendons)
57
Where are collagen types I, II, III, V, and XI found?
In interstitial connective tissue
58
What collagen types form the major stress bearing component of cartilage, tendons and ligaments?
Types I, II, III, V and XI
59
What type of collagen is the most abundant?
Type I
60
Where is type I collagen found?
In most connective tissue
61
Type I collagen is a major component of what structures?
``` Bone Tendon Skin Dentin Ligament Fascia Arteries Uterus ```
62
Type II collagen is a component of what type of cartilage?
Hylaine cartilage
63
Where is type III collagen found?
Skin Arteries Uterus
64
What type of collagen is prominent in periodontal ligament?
Type III collagen
65
Which type of collagen is absent or in very low levels in bone?
Type III collagen
66
What are the basement membrane collagens?
Types IV, VIII and X
67
What type of collagen is the most abundant structural component of basement membranes?
Type IV
68
What makes type VIII collagen?
Endothelial cells
69
What make type X collagen?
Chondrocytes during endochondral ossification
70
What are the two types of multiplexins?
XV | XVIII
71
Where are types XV and XVIII found?
In basement membranes
72
What type of domains to multiplexins have?
Triple helix domains and interruptions
73
What are fibril associated collagens with interrupted triple helices (FACIT)?
Large multidomain molecules with 2 or more short helical rods, separated by small, non-triple helical domains
74
FACIT collagens have large what?
N-terminal non-collagen-helix-domain
75
What are the FACIT collagen numbers?
``` IX XII XIV XVI XIX ```
76
Where is type IX collagen found?
Cartilage and certain embryonic tissues
77
Where is type XII collagen found?
Similar to type I collagen, so it is found in many connective tissues
78
What types of cllagens have several fibrocectin and von Willebrand domains?
XII and XIV
79
What shape is type VI collagen?
Dumbell-shaped with short helical domain and large globular domain at each end
80
Where are type VI collagens found?
Ubiquitous in connective tissue
81
Where are type VI collagens especially abundant?
Cornea
82
What is the longest type of collagen with a triple helix?
Type VII
83
Where are type VII collagens found?
Anchoring fibrils of basement membrane underlying stratified epithelia
84
Collagens are ___ ___.
Secreted proteins
85
Where does translation of collagen alpha-chain mRNAs take place?
On the rough ER
86
What are the steps of collagen synthesis?
1. Nascent polypeptide chain enters lumen of RER 2. Signal peptide cleaved off to give procollagen alpha-chain 3. Hydroxylation of proline and lysine in RER lumen 4. Hydroxylated lysines can be glycosylated 5. 3 alpha-chains linked by disulfide bonds at C-terminal; starts procollagen triple helix formation 6. Procollagen molecules packaged into secretory granules and secreted
87
In collagen synthesis, what occurs in the preprocollagen to procollagen step?
``` Signal peptide cleaved Registration peptides Attach OH to Pro & Lys Attach sugars to hydroxy-lys Form triple helix Package into vesicles ```
88
In collagen, what occurs in the procollagen to tropocollagen step?
Registration peptides cleaved to form insoluble tropocollagen Tropocollagen aggregates to form fibrils Fibrils crosslink
89
What are N and C terminals in collagens?
Extension called registration peptides that must be proteolytically removed by extracellular enzymes
90
What do procollagen registration peptides prevent?
Further assembly of collagen molecules into multimers prior to secretion
91
After secretion, what removes registration peptides?
Specific procollagen N and C peptidases
92
How is a mature collagen molecule yielded?
After secretion, the registration peptides must be removed
93
What is a mature collagen molecule called?
Tropocollagen
94
What can crosslink the modified lysine side chains of collagen?
Lysyl oxidase
95
What is needed for full strength in collagen?
Cross-links
96
Do cells only secrete one type of fibrillar collagen type?
No - they can secrete multiple types
97
With heterogeneous fibrils it is believed that there are 3 types of collagen involved. What are they and how are they structured?
Collagen V is the core of the fibril | Types I & II polymerize around it
98
What forms the fiber core of collagen II fibrils?
Type XI collagen
99
What regulates fibril morphogenesis?
Core collagens
100
What give mechanical strength to fibrils?
Bulk collagens
101
What type of domain does collagen IV have?
Relatively long triple helical domain
102
How is flexibility generated in collagen IV?
Sever small interruptions generate flexible rod
103
What is assembly of collagen VI?
assembles into beaded filaments
104
What does collagen VI promote?
attachment of fibroblasts and binding to other collagens (widely distributed)
105
What are the beaded filaments associated with in collagen VI?
globular domains
106
What does collagen VII do?
dimerizes by antiparallel overlapping
107
How are dimers arranged in collagen VII?
dimers associated laterally to form 800nm long bundles of fibrils (microfibrils) in basement membrane
108
What type of collagen has an N-terminal domain at each end of that fan out and interact with other ECM components?
collagen VII
109
What type of unique collagen is found in hemidesmosomes of epidermal-dermal junctions?
collagen XVII
110
What kind of protein is collagen XVII?
a transmembrane protein
111
When are tissues remodeled?
during normal development, bone growth, and wound healing
112
How do enzymes degrade collagen?
specific collagenases hydrolyze collagen peptide bonds that causes fragments to denature and release single chain fragments
113
What type of peptide is much more susceptible to degradation?
an open conformation peptide
114
What is cleaved denatured collagen called?
gelatin
115
What are gelatinases?
denatured collagen that has been further degraded by a variety of enzymes
116
What are some examples of matrix metalloproteinases (MMPs)?
collagenase, gelatinase, stromelysin (proteoglycans)
117
What is fibronectin?
a ubiquitous ECM glycoprotein
118
What are some characteristics of fibronectin?
soluble form in body fluids, insoluble form in ECM, especially basement membranes
119
Where does fibronectin play a major role?
in embryogenesis, wound healing, hemostasis, thrombosis
120
Fibronectin is a modular protein that is comprised of what three different modules?
Fn1, Fn2, Fn3