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Flashcards in ECM Deck (72):

What are the functions of ECM

1. Provides support for cells and cell layers (anchors cells to underlying stromal CT)
2. Acts as a barrier: impedes the passage of cells
3. acts as passive selective molecular seieve bet tissue compartments
4. acts as a solid phase reg of cell attachment, growth and diff
5. Modulates the mineralization process


What components can ECM be divided into

1. fibers
2. amourphous ground substance
3. basement membrane


What are filaments

threadlike structure; smallest in diameter; typically a single molecule or linear chain of molecules


What are microfibrils

an aggregate of filaments


what are fibrils

aggregate of microfibrils; first thing we can see on EM


what are fibers

an aggregate of fibrils


What can fibers be divided into

1. Elastic
2. collagen


what is ground substance made of

glycoproteins, glycosaminoglycans, proteoglycans


Proteoglycans are in a bunch of diff ____and in diff ____-

tissues; amounts


The types of cells that secrete ECM are:



Enamel is the only ECM that is secreted by an ____type of cell



What are specialized CT's:

1. cartilage: chondroblasts
2. bone: osteoblasts
3. dentin: odontobasts
4. enamel: ameloblasts
5. Basement membrane: epithelia, muscle, fat, Schwann cells


______is the most abundant protein of the body

collagen; skin has the most, (75%), then cartilage (50%) then coricol bone (25%)


Collagen facts:

1. Left -handed helix; not a true alpha helix!
2. Proline ring structure adds rigidity
3. no Trp or Cys in mature form, not nutritious.
4. high content of OH-pro/OH-lys is useful for quantifying collagen content


What is the structure of collagen

1. 3 helical strands wrap around each other = TROPOCOLLAGEN
2. Tropocollagen fibrils arrange themselves in staggered array of parallel bundles.
3. alignment of every 4th molecule causes striations, visible by EM
4. Crosslinks via lysinonorleucine!


Lysinonorleucine is a _____aa and requires the enzyme ____ ____ ____ which requires Vitamin ___ as a cofactor

nonstandard; lysyl amino oxidase; Vitamin B6


What are the classifications of collagen

1. Some form typical fibers
2. Some just form microfibrils that dont assemble into fibers.
3. Each collagen molecule consists of three alpha chains
4. 34 diff alpha chains known: collagen family


What are the 5 types of collagens

1. Fibrillar: form long fibers with high tensile strength.
2. Non fibrillar:
-Basement membrane collagens (network forming)
-Fibril-associated collagen with interrupted triple helix (FACIT)
-Microfibrillar colalgen


How are collagen families grouped

Group chains into 28 diff subfamilies based on ability to interact to form triple helices.
-Diff members of subfamily denoted by subscript


What are the fibril forming collagens

I, II, III, V, and XI; they assemble into bundles.


WHat is type I collagen

the most abundant; found in most CT and is a major component of :
1. bone
2. tendon
3. skin
4. dentin
5. ligament
6. fascia
7. arteries
8. uterus


Where is type II collagen found

component of hyaline cartilage and is found in articular surfaces


Where is type III collagen found

Made up of reticular fibers and is found in skin, arteries, uterus, prominent in periodontal ligament and there is a very low level in bone.


What is Type IV basement membrane collagen

Found in lens of eye and is the most abundant structural component of basement membranes


What are FACIT collagens

-Large multidomain molecules
-have two or more very short helical rods sep by small non triple helical domains
-Have large N-terminal non collagen helix domain


What are two types of FACIT collagens

1. Type IX: cartilage and certain embryonic tissue
2. Type XII: similar distribution to type 1 collagen (many CT)


Describe Type VI microfibrillar collagen

dumbell shaped molecule with short helical domain and large globular domain at each end. Its ubiquitously distributed in CT and especially abundant in CORNEA


Describe Type VII microfibrillar collagen

-Longest triple helix of the collagens
-Found in anchoring fibrils of BM underlying stratified epithelia
-N-terminals of each chain folded into arms and contain vWF and fibronectin repeat domains
-C-terminal has small globular domain involved in microfibril assembly


How is collagen formed?

1. Starts at ER called preprocollagen.
2. Attach OH to Pro and Lys
3. Attach sugars to hydroxy-lys
4. Form triple helix
5. Package into vesicles
6. Tropocollagen formed after registration peptide cleaved off and forms fibrils
7. fibrils crosslink


Where is lysyl oxidase formed. Where is proline hydroxylase formed?

extracellular space; intracellular space


What is Collagen XVII

1. Anchoring fibrils found in hemidesmosomes of epidermal-dermal junction
2. Transmembrane protein
3. N terminal in cytoplasm
4. C terminal flexible extracellular rod.


How is collagen degraded

1. Specific collagenases hydrolyze collagen peptide bonds. -->fragments denature and release single chain fragments
2. Cleaved denatured collagen called gelatin.


What is fibronectin

Ubiquitous ECM glycoprotein:
1. soluble form in body fluids
2. insoluble form in ECM, esp BM
3. Plays a major role in embryogenesis, wound healing, hemostasis, and thrombosis


What is RGD

3 aa sequence: argenine, lysine, and aspartate; they bind to cells by binding to integrins (cell transmembrane rec proteins that interact with ECM)


Fibronectin is also a ____protein. It is comprised of 3 diff modules

modular; it provides binding sites for cells, ECM components, blood proteins and GAGs


What is the fibronectin network like

secreted as a dimer of 2 large monomers held by disulfide bonds.


What regions interact to form fibronecting meshwork

1. N terminal heparin binding domain
2. RGD cell binding domain
3. first Fn3


What are features of elastic fibers

1. Forms triple member tropoelastin that complex into fibers.
2. Desmosine crosslinks that make it stretchy
3. Rich in glycine, alanine, and lycine
4. Not a true alpha helix


____also makes up elastic fibers and is loc on periphery, in interior of elastic fiber, free in ECM



_____also associated with elastic fibers and have domains that have homology to EGF. It is a coating in elastic fibers which is found in

Fibrillins; heart valves and big blood vessels.


What are features of BM

1. Structureless that is subjacent to basal surface of epithelia, kidney glomerulus and lung alveoli.
2. produced by eptithelial, endothelial and many mesenchymal cells


The part closest to epithelial tissue is called ____The part that is closest to connective tissue is called_____

basal lamina; reticular lamina:


What makes up the basal lamina

lamina lucida, lamina densa


What does reticular lamina look like

Its underneath basal lamina and has collagen fibers; Have hemidesmosomes.


What are BM glycoproteins

1. Laminin
2. Nidogen/Entactin
3. Fibulins


What are laminins

Most typical and abundant non collagenous glycoproteins of BM
-looks like a cross
-made up of alpha, betta and gamma polypeptides


What do laminins form

polymeric scaffold through calcium mediated interactions bet domains in short arms of cross.
-binds to heparin, collagen type 4, and nidogen


What is nidogen

dumbell shaped molecule with laminin/collagen IV binding domain at one end, self aggregating domain at other, sep by rod like connecting domain. It dimerizes then cross links with laminin and collagen IV


What are fibulins

1. Relatively abundant BM glycoproteins, that contain 9 EGF like repeats. Thought to link cells to BM


WHat is tenascin

found in oral cavity. Upregulared during periods of wound wealing. Has multiple Fn3 domains, and may help in cell migration bcit has anti adhesive domain that help cells move.
-6 subunits, star shaped arrangment, held together by Disulfide bonds


if cell binding then you have:

RGD receptors


what form hemidesmosomes

integrins, collagen 17, and transmembrane proteins


Mechanical movement of the ECM is sensed by intracellular molecules such as the ____components via changes in _____conformation. Signals are also transduced to the nucleus by clusters of integrins called ____ ____ and a ____associated with them.

cytoskeletal; integrin; focal adhesions; FAK


What are considered mineralized tissues

1. bone
2. enamel
3. dentin
4. cementum
(formed by deposition of hydroxyapetite crystals of specialized ECMs)


What are features of bone

1. formed by osteoblasts and deposition of hydroxyapetitie crystals into a specialized ECM.


What are membrane bones? what about endochondral bones?

1. osteoblasts secrete matrix that become mineralized
2. cartilage model is removed and replaced with new matrix made by osteoblasts.
-replacement req ECM remodeling which is secreted by osteoclasts.


Bone is ___percent collagen Type 1.



What are the non collagenous proteins in bone

1. acidic glycoproteins
2. some are phosphorylated
3. some contain Gla residues (gamma carboxylate glutamate impt for calcium binding)
4. some are proteoglycans


What is an ex of a non collagenous bone protein

1. Osteonectin (SPARC): Present in ECM of all bone
-has low levels in dentin
-binds Ca, hydroxyapetitie and collagen
-important in bone formation but role unclear


what is an ex of another non collagenous bone protein

Osteopontin (bone sialoprotein I, BSP I)
-Acidic bone glycoprotein, low levels in dentin, cementum
-contains phosphoserine and poly ASp sialic acid
-high affinity for calcium
-contains RGD sequence
-involved in attaching osteoblasts to osteoid.


What is bone sialoprotein (BSP II)

Non collagnous bone protein:
1. 50% carbs
2. contains stretches of polyglutamic acid
3. high Ca affinity
4. RGD sequence
5. Marker for early stages of mineralization
6. Made by osteoblasts, odontoblasts, low levels by chondrocytes.


What are osteocalcins

Non collagenous bone protein
-binds Ca with high affinity and adheres to hydroxyapatite crystals
-found in bone, dentin, and cementum
-Though to be involved in reg crystal growth


WHat is dentin

Predentin becomes mineralized by hydroxyapetite deposition to form dentin.
-Dentin type 1 collagen differs than skin collagen bc it has 3 x more hydroxylysine, more cross-linked, has loose knit packing of filaments in fibrils.
-No type III collagen as opposed to skin


Dentin-sialophosphoprotein (DSPP) is a _____for dentin that can get processed into ___ and DGP

precursor; DPP


What is the most abundant protein in dentin after collagen

-can bind large amounts of calcium at high affinity
-will bind collgen
-involved in initiating mineralization in circumpulpal dentin


What is dentin sialoprotein

Recently discovered dentin non collagenous protein
-contains glycoprotein
-thought to be inv in regulating mineralization


Enamel has less than 1% organic material. Its the only mineralized tissue made by

epithelial cells (ameoblasts); unlike other mineralized tissues, hydroxyapetite crystals are not deposited in a collagen matrix (no hydroxyproline!)


What are amelogenins

proteins secreted by ameloblasts into dev enamel during amelogenesis; over 90% of enamel protein content
-coded on X and Y chromosomes
-degraded by proteinases during mineralization
-Tyrosine rich amelognin peptide fragment incorporated into enamel
-Thought to be involved in regulating organization and growth of enamel crystals


Amelogenin forms ____which are kind of like actin. Its a globular protein that self assembles into fibers which is the driving force for formation of parallel bundles of apatite during enamel formation and reg's calcium phosphate crystal growth.



What are enamelins

1. enamel specific proteins
2. hydrophilic
3. left behind in enamel after mineralization complete
4. Can only be extracted by dissolving material
5. Interacts with amelogenin; may stabilize amelogenin oligomers and affect interaction with mineral phase


what are enamel proteases

1. MMP -20 (enamelysin): only tooth specific MMP, processes amelogenin; promotes amelogenin self-assemby
2. Kallikrein-4: Further digest proteolytic products of amelogenin and enamelin. Required for proper mineralization and hardening of enamel during maturation.


what is cementum

1. Thin layer of calicified tissue covering root surface of teeth
2. like dentin, bulk is type 1 collagen
3. unlike dentin, contains type III collagen as well