ECM and cell adhesion Flashcards
Which macromolecules are found in the ECM?
fibrous proteins and glycosaminoglycans
What makes the ECM so different in various tissues?
- The diveristy of proteins and carbohydrate components of the ECM
List the different functions of the ECM
- Adhesive substrate (tracks to direct migratory cells)
- Provides structure (tissue bounderies)
- Presents growth factors to there receptors
- stores growth factors
- senses and transduces mechanical signals
Which parts of tissues make up the ECM?
interstitial matrix and basement membrane
How does the ECM resist compression?
polysaccharide gels and fibrous proteins fill the interstitial space
What percentage of the total proteins in the body does collagen form?
25%
What is the structure of collagen?
Triple helical structure formed by 3 peptide chains.
Every third amino acid is glycine, the smallest side chain able to fit into the crowded central core.
Has a Gly-X-Y sequence. X and Y can be any acid but X is often proline and Y is hydroxyproline.
Describe the function and location of Fibillar collagens
Function- Provide tensile strength
Location- tendons,ligmanets,skin
Describe the function and location of non-Fibillar collagen?
Function- Lattice-forming. Major structural component of basment membranes
What are basement membarnes? What is there function?
Thin layers of ECM
Function- Anchor cells to surrounding connective tissue
-Filtration
What is the function of collagen V?
Regulates the diameter of collagen type 1 fibrils
What is Osteogenesis imperfecta?
Brittle bone disease
Caused by mutations affecting the synthesis of type 1 collagen
Mutations mainly single base substitutions which convert glycine in the Gly-X-Y to a bulky amino acid preventing the correct folding of the collagen fibers into triple helix
Why are bones most affected in Osteogenesis imperfecta (brittle bone disease)
Collagen type 1 is dominant in bone
Which protein is predominant in elastic fibers?
Elastin
What makes elastin flexible?
Weak hydrophobic interactions between valine residues
Name 1 similarity and 2 differences between collagen and elastin?
Similarity- both rich in glycine and proline
Differences- elastin is more hydrophobic
In elastin 1 in seven is valine
Which glycoprotein covers Elastin?
Fibrillin
What causes marfan syndrome? Name 2 symptoms
Mutation in fibrillin gene
Tall stature, long arms and legs, loose joints, deformed spine. Floppy mitral vaalve and the arotic walla is prone to rupture
What are the 2 main sugar containing proetins?
Glycoproteins and proteoglycans
What are the functions of glycoproteins?
- receptors for hormones
- cell-cell intercations
- provide strength and support to ECM
What are proteoglycans?
Gel forming part of the ECM
Composed of petide chinas and carbohydrates
What is the function of proteoglycans?
provide structural support to tissues, especially cartilage and connective tissue
Describe the sturcture of the proteoglycan found in cartilage
Large aggregates composed of chondroitin sulfate and keratin sulfate chains linked to core proteins form a jelly like matrix
How does water enter the ECM?
Because of the negtaive charge of proteoglycans, counter ions are required to maintain electrical neutrality. These ions draw water into the ECM. Causing the matrix to swell and stiffen. = tension between osmotic forced and binding interactions between proteoglycans and collagen
What do proteoglycans do to growth factors?
The control the bio-avalibility and store them
Which cellular processes are regulated by cell adhesion?
- Signal transdution (cells detect and respond to change)
- cell migration
- tissue development
What is the name used for cell adhesion molecules? State all the different types
CAMS
integrins, immunoglobulin (Ig) superfamily, cadherins, and selectins
Which CAMS are homophilic and heterophilic?
Homophilic- Cadherins and immunoglobulins (bind to the same type of CAM)
Heterophilic- integrins and selectins (bind to different types of CAMS)
What are intergrins?
Plasma membrane proteins which transmit mechanical signals between the ECM and intracellular space
Which factors help guide cell migration?
External signals-
- chemical signals
- Mechanical signals
What happens if a cell migrates on a flat substrate without ECM?
Detachment and apoptosis
Describe the 4 stages in cell migration
- Polymerization of actin filaments at leading edge gives a protrusive force.
- New adhesions are rapidly linked to the actin filaments.
- Retrograde actin movment and contractile foces pull cell body forward
- Contractile network forces and actin filaments retract the tailing cell edge
What is Leukocyte extravasation?
The movement of leukocyte into the cell caused by infection or inflammation.
Leukocyte binds to ICAM-1 which stops it rolling and starts migrating into the injured cell
What helps cancers metastasis?
Cleavage if cell adhesion occurs. e.g. Cadherins inactivated via genetic mutation
Activation of growth factors and cytokines also helps them migrate
