ECM Flashcards
Ground substance:
- Water, ions, and macromolecules in the ECM
Ground substance + cells =
connective tissue
The basal surface of the epithelium of most tissues is underlain with:
- basement membranes
- sheets of ECM that separate cells.
The 3 layers of basement membrane that can defined at EM level and that are enriched in specific ECM components:
- lamina rara/lucida/interna
- lamina densa
- lamina reticularis.
Schematic of basement membrane organization:
There is a continuum (no clear boundary) between the ECM and the cell due to:
- integrins
- syndecans
ECM components in lamina rara/lucida/interna:
- laminin 5
- type XVII collagen
ECM components in lamina densa:
- laminin 1
- type IV collagen
- perlecan
ECM components in lamina reticularis:
- made primarily by fibroblasts
- type III collagen
Stroma:
- Major component of adult ECM
- located outside the lamina reticularis of basement membrane
- secreted by fibroblasts and specialized mesenchymal cells
What ECM components are in the stroma?
- fibronectin
- collagen types I, III, VII
- elastic fibers
Characteristics and function of collagen:
- provides tensile strength
- resistant to stretching
- most abundant protein in body (25% of all)
Collagen structure:
- Triple-stranded helical molecules containing three monomer α-chains wrapped around each other
- imparts strength to the molecule
α-chain amino acid composition of collagen:
Repeating Gly-X-Y
- Glycine present as every third amino acid
- Gly-H side chain fits inside helix
- if altered, helix unstable
- X and Y are often proline and lysine
- hydroxylated forms can H-bond
- lysine can be de-aminated to cross-link
The four classes of collagen:
- fibril-forming (fibrillar) (types 1-3, 5, 11)
- fibril-associated (types 9, 12)
- network-forming (types 4, 7)
- transmembrane (type 17)
The three important fibril-forming collagens:
- Type I
- Type II
- Type III
Type I collagen:
- most abundant (>90% all collagen)
- in tendons, bones, lungs, skin
Type II collagen:
- cartilage (50% cartilage dry weight)
Type III collagen:
- widely distributed
- skin, aorta
- stained with silver
Steps in the biosynthesis of fibril-forming collagens (9):
- synthesis of PRO-α-chain (RER)
- signal peptide removed (golgi)
- hydroxylation of select prolines and lysines (golgi)
- glycosylation of select hydroxylysines (golgi)
- self-assembly of 3 PRO-α-chains (golgi)
- procollagen triple helix formation (golgi)
- secretion from golgi to ECM (vesicle)
- cleavage of propeptides (ECM)
- self-assembly into fibril (ECM)
Vitamin C and collagen biosynthesis:
- Vitamin C required as co-factor for hydroxylase.
- Deficient = scurvy
- hydroxylation does not occur and collagen α chains degraded.
Steps in formation of tropocollagen:
- After secretion for Golgi, extension peptides (pro peptides) of fibril-forming collagen molecules (types I, II, III) are cleaved.
- cleaved propeptides = tropocollagen
- fibril assembly then occurs
Why do Type III collagen “reticular” stain with silver?
- more carbohydrates
- thinner fibrils
- more branched
- few bundles
What is this an image of?
Type III collagen “reticular” stained with silver
What is this an image of?
- collagen fibrils in EM
- note striations
- Types I, II, III, V, and XI can form fibrils
Function of fibril associated collagens:
- decorate outside of fibrils
- have some interruption of triple helix
- less rigid; can bend and form “hinge”
- functionally important for joint integrity
Fibril Associated Collagen Type IX:
- Decorates outside of Type II collagen of chondrocytes (cartilage)
- interruption in helix - less rigid - forms hinge
- important for joint integrity
What are the two major types of network forming collagens?
- type IV and type VII
EXTENSION PEPTIDES NEVER CLEAVED IN NETWORK FORMING COLLAGENS
Type IV Collagen:
- network forming collagen
- major component of basal lamina (lamina densa)
- multiple regions where triple helix is interrupted
- extension peptides not cleaved
- C-TERMINUS FORMS CHICKEN-WIRE ARRAY.
- N-TERMINUS ALLOWS MULTI-LAYER BINDING.