Extracellular Matrix Flashcards
What is the ECM?
Filler and macromolecules (secreted by the cell)
Functions of ECM
- Cellular division
- Motility
- Differentiation
- Adhesion
- Structure
3 classes of ECM components
- Structural proteins
- Proteoglycans
- Adhesive glycoproteins
Examples and functions of structural proteins
Collagens and elastins → provide strength and flexibility
Proteoglycans
What are they:
Function:
Protein-polysaccharide complexes
Provide matrix for structural proteins
Examples and function of adhesive glycoproteins
Fibronectins and laminins → attach cells to matrix
______ is the most abundant protein in vertebrates and it contains __% of total body protein
Collagen → 25-30%
Tendons and ligaments contain a lot of?
Collagen
Collagen structure
Rigid triple helix of polypeptide chains
Collagen strength
1 mm fiber can hold 20 lbs
__ different alpha chains combine to form __ types of collagen
Which are most abundant?
25 different alpha chains → 15 types of collagen
I, II and III most abundant
Type I composes __% of collagen in body
90%
Collagen cross linking function
Strengthens collagen bundle to withstand high stress
Elastin provides flexibility to what tissues?
- Lungs
- Heart
- Arteries
- Skin
- Intestines
- Ears
Elasticity is dependent on what ratio?
Collagen : Elastin
Elastin composition
Proteins rich in glycine and proline (no hydroxylation) and elastin molecule (crosslinked between lysines)
Proteoglycan composition
Glycoprotein + glycosaminoglycan side chain
GAGs
Long polysaccharides → 2 monosaccharides in alternating order
Glycoprotein
Protein with GAGs (up to 95% carbohydrate)
How are proteoglycans classified?
And what are 3 of the most common?
By glycosaminoglycan side chain:
- Chondroitin sulfate
- Keratan sulfate
- Heparin / heparin sulfate
Location of chondroitin sulfate
Cartilage (osteoarthritis implications)
Keratan sulfate locations and function
- Cornea
- Cartilage
- Bone
Cushion
Proteoglycan functions
- Receptors
- Filtration
- Shock absorption
- Trap water (>50%x their weight)
Hyaluronate functions:
- Lubricates joints
2. Found on surface of migrating cells → facilitates cell migration
Heparan sulfate
What is it:
Location:
Family with side chains made of D-glucosamine or L-iduronic acid
Found in every cell of body
Heparin
What is it:
Function:
One member of the heparan sulfate family
Anticoagulant
Heparan sulfate family functions (other than heparin)
- Bind growth factors
- Important role in inflammation
- Entry of virus into cells (herpes, rabies)
Fibronectin
Most common adhesive glycoprotein (contains about 5% carbohydrates)
Family of closely related proteins
Fibronectin solubility
Can be soluble, insoluble or partialy soluble → caused by alternative splicing of the same gene
Fibronectin roles
- Maintain cell shape
- Possible role in cancer
- Blood clotting (soluble form)
- Wound healing → guides immune cells to wound
- Cell migration
Laminins are mainly located where?
Basal laminae
Basal lamina
Separates ECM from epithelial cells
Basal lamina roles
- Structural support
- Permeability barrier (acts as filter in kidney)
- Cell migration (may allow migration of cancer cells)
Matrix remodeling is most active at?
Sites of abundance-cellular sources:
- Cartilage: chondrocytes
- Bone: osteocytes, osteoblasts
- Tendon: teniacytes (fibrocytes)
- Cornea: fibrocytes
Enzymes which degrade ECM
- Metalloproteinases
2. Serine proteases:
2 ways to stop ECM degradation
- Tissue inhibitors of metalloproteinases (TIMP1, 2, 3, 4) → ireversible
- Serine protease inhibitors
Polypeptide chains found in collagen are high in?
- Glycine
- Hydroxylysine
- Hydroxyproline
Metalloproteinases
Specific for 1 ECM component
Requires zinc or calcium
Serine proteases
Cleave protein sequences at serine residues → work with metalloproteinases
Fibronectin’s role in cancer
Carcinomas are unable to synthesize fibronectins → cell detaches from ECM
Type I collagen is found where?
- Skin
- Bones
- Tendons
- Ligaments
Collagen cross linking with aged animals
Can become abnormal → loss of joint function
2 forms of hyaluronate
Proteoglycan (backbone in cartilage) or free molecule
Basal lamina surrounds what types of cells?
- Muscle
- Fat
- Schwann cells
Composition of basal lamina
Thin sheet (50 nm) of EC material