Connective Tissue Flashcards
3 cell types responsible for making connective tissue matrix
fibroblasts
chondrocytes
osteocytes
fibers (collagen, elastin, fibronectin, etc) in a hydrated gel (glycosaminoglycans + H2O) and growth factors / support proteins
matrix
How does ECM regulate cell behavior?
Cells adhere to and migrate differently on different ECM
ECM can bind and regulate growth factors
**ECM can itself act like growth factors. Cell have receptors for, and respond to ECM.
Densely packed collagen fibers, somewhat wavy but mostly parallel. Scanty fibroblasts wedged between fibers.
(tendons and ligaments)
Dense regular connective tissue
Dense collagen fibers, closely packed, but running in all directions
Few cells
(dermis)
Dense irregular connective tissue
Fewer and thinner collagen fivers, more space (watery gel) between
More cells
(hypodermis, lamina propria)
Loose (areolar) connective tissue
Special term for loose CT beneath a mucous (moist) epithelium - GI tract, respiratory, etc.
Lamina propria
Collage fibers are made of densely packed bundles of collagen ________ that cannot be resolved with a light microscope
Fibrils
Form 67nm banding pattern
About 50-150 nm in diameter
About 100 make bundles that are fibers
Collagen fibrils
In a collage triple helix, three collagen _______ chains are wrapped around each other, and support each other in a near maximally extended form.
alpha
Describe a collagen molecule
trimer
very long, thin
very limited stretch
rigidity of plexiglass
Characteristic signature of collagen chain
Every third aa is glycine
Gly needs to be in the center when three alpha chains come together
Closely packed center
Protein-protein bonds are _____________ and reversible (hydrophobic bonds)
non-covalent
The strength of the bond is roughly proportional to the ____________ of the contact interface.
surface area
Why is collagen made with a 67nm staggered overlap?
Increase surface area and strength
What is the hierarchy of collagen substructures from molecules to tendon?
Alpha chain Collagen molecule Fibril (staggered overlap) Fiber Tendon
How are fibrils and fibers stalinized once non-covalently self-assembled?
Intermolecular covalent crosslinks
How is triple helix assembly lined up and fibril formation prevented until properly distributed in ECM?
Propeptides
allow for assembly, but block fibril formation due to bulkiness
List the steps for collagen processing and assembly that occur in the RER and golgi before secretion.
- Synthesis and translocation of pro alpha chain into RER
- Hydroxylation of selected pro and lys
- Assembly of C-propeptides of three alpha chains **aligns the alpha chains
- Folding of the triple helix, from C to N term. (only begins are C-propeptide fold)
- Formation of N-term propeptide finishes the procollagen molecule
List the steps in fibril assembly following secretion.
- The N and C term pro peptides block assembly of the secreted procollagen molecules.
- Two enzymes, procollagen N and C-peptidase cleave the pro peptides.
- Once the propetides are released, the collagen molecules are active for assembly. They spontaneously self assemble into long, 50 nm diameter fibrils. (staggered)
- The fibrils aggregate side to side to form fibers.
- Covalent crosslinks are added to stabilize fibrils and fibers.
Why are blood vessels affected before tendons during vitamin c deficiency (scurvy)?
Tendons turn over more slowly
Align three alpha chains prior to folding triple helix
Block assembly of fibrils until molecules are properly deposited in ECM
In non-fibrillar collagens (Type IV), used for assembly
Pro-collagen peptides
Possible combinations for three alpha chains in molecule
three different (3 genes) three identical (one gene) - Type 1 two identical, one different (2 genes) - Type II, IV
Type of collagen found in skin, tendon, bond ligaments, cornea, internal organs (most of body’s collagen)
Type I
Type of collagen found in cartilage, intervertebral disc, notochord, vitreous body of eye
Type II
Type of collagen found in basement membrane, and specialized basement membrane of kidney (glomerular BM)
Type IV
Found between epithelium and CT, surrounding muscle cells, and between two cell layers in the kidney (filtration barrier)
Basement membrane (basal lamina)
3 components of basement membranes
Collagen type IV
Laminin
Proteoglycans
Froms a 2-D net (not fibrils)
A major structural component of basement membranes
Cell adhesion
**Binds integrin receptors
Collagen type IV