EXTRACELLULAR MATRIX AND CELL ADHESION Flashcards
What is the ECM?
Complex network of secreted macromolecules- fibrous proteins and GAG’s
- Located the extracellular space secreted by cells
- Provides structural and biochemical support to the surrounding cells
What are the functions of the ECM?
- Provides a 3D framework for the organization of tissues
- Defines tissue boundaries
- Provides integrity and elasticity to developing organs
- Degraded by invasive cells during development and disease - Regulates proliferation, differentiation, migration and cell to cell interaction
- Functions as a adhesive substrate
- Directs migratory cells
- Creates concentration gradients for haptotactic migration - Presents growth factors to their receptors
- Controls spatial distribution of ECM-bound surface molecules
- Facilitates communication between growth factor receptors and and ECM receptors - Separates and stores growth factors
- Allows for spatio-temporal regulation of GF release
- Organizes morphogen gradients (a mechanism by which the emission of a signal from one part of an embryo can determine the location, differentiation and fate of many surrounding cells.)
- Releases GF in the presence of cell-mediated forces or proteolytic degradation - Senses and transduces mechanical signals
- Defines mechanical properties instructive to cell differentiation
- Activates intracellular signalling through interaction with cell surface receptors
- Engages cytoskeletal machinery and synergizes with growth factor signalling
What is the ECM composed of?
It is made by cells that produce collagens, elastin, glycoproteins and proteoglycans
- Macromolecules form 3D gelatinous bed
- Changes in ECM characteristics are associated with chronic disease
What are collagens?
Most abundant protein in the body
- Primary structural component in connective tissue
- Made up of related but distinct peptide chains
- Triple helical structure formed by 3 peptide chains
- Every 3rd amino acid is glycine (Gly-X-Y)
What are two main types of collagen?
- Fibrillar
- Well-organized banded fibrils
- Major component in tendons, ligaments and skin
- Provides high tensile strength - Non-fibrillary
- Forms microfibrils or mesh-like structures
- Structural components of basement membranes
- Anchorage of cells and filtration
Type I collagen
- Fibril forming
- Found in tendons, skin, bone cartilage, connective tissue and teeth
Type II collagen
- Fibril forming
- Found in cartilage
Type III collagen
-Found in muscles, organs, arteries and reticular fibres
Type IV collagen
- Non-fibrillary
- Found in basal lamina
Type V collagen
-Found in bone matrix and the cornea
What is Osteogenesis imperfecta (OI)?
Osteogenesis imperfecta (OI) is an inherited (genetic) bone disorder that is present at birth. It is also known as brittle bone disease
- A child born with OI may have soft bones that break (fracture) easily, bones that are not formed normally, and other problems
- Caused by genetic defects in collagen type I synthesis
- Characterized by fragile bones, thin skin, abnormal teeth, thin sclera and weak tendons
- Single base change mutations (converts glycine to bulky amino acids, preventing correct folding of collagen chains to form fibrils)
What are the types of osteogenesis imperfecta?
- Type I
- Autosomal dominant
- Most common type
- Mildest type
- COL1A1 and A1 genes - Type 2
- More severe type
- New mutation
- Dominant if affected individuals survive
What is elastin?
Predominant protein of elastic fibres
- Gives flexibility required for blood vessels, lungs, ligaments and skin
- Can stretch in 2D
- Rich in glycine and protein
- Has more valine than collagen which interacts with hydrophobic domains, giving it elasticity
- Covered by the glycoprotein fibrillin which gives it stability
What is Marfan syndrome?
MFS is a genetic disorder that affects the connective tissue. Those with the condition tend to be tall and thin, with long arms, legs, fingers, and toes. They also typically have overly-flexible joints and scoliosis.
- Rare genetic disease
- Mutations in the fibrillin gene
- If fibrillin is absent or misfolded, it would lead to changes in ECM properties
- Symptoms: Tall stature, long arms and legs, arachnodactyly (spider fingers), loose joints, floppy cardiac valves, eye problems (lens dislocation), aortic aneurysms
What is the function of fibrillin in elastin fibres?
- Anchors elastin fibres to other ECM proteins
- Modulates binding and sequesters growth factors, controls the amount of TGF-Beta
- In Marfan syndrome, the TGF-B is not bound with ECM, it accumulates in the lungs, heart and other tissues which changes the ECM
