Lecture 3 - Quiz 1 Flashcards
What is the ECM?
Extracellular matrix - any substance produced by cells and secreted to the extracellular space within the tissues - connective tissue
What are fibroblasts and their structure?
Fibroblasts have elongated nuclei and cytoplasms, and synthesize and maintain all the ECM components
What are tenocytes?
The fibroblasts of the tendons that maintain the ECM - principally collagen
What gives ECM tension and compression resistance?
Collagen crosslinks for resistance to tension and proteoglycans give resistance to compression
What are the roles of ECM?
Hold tissues together for structural support, comportmentalize tissues from one another and regulate intercellular communication by cell signaling - promotes and inhibits growth factor signals - essential for growth and wound healing
How does the ECM promote and inhibit GF signals?
Promotes by pericellular matrix (PCM) molecules binding and localizing GF close to cell surface to promote binding to receptor, in hibits when ECM/PCM molecules bind GF and sequester it away from the receptors
What is the structure of the PCM for chondrocytes?
PCM made up of hyaluronic acid with red blood cells kept at a distance from the chondrocytes
What are the components of the ECM?
Ground substance - like adhesive glycoproteins like laminin and fibronectin play a role in the adhesion of the cells and glycosaminoglycans (GAGs) give a hydrate gel for resistance to compressive forces and fibers - provide tensile strength and elasticity with collagens and elastins
What are the classifications of GAGs?
Heparin, chondroitin, keratan - all sulfates to give negative charge to bind a lot of water
Hyaluronic acid HA - non sulfated
Make up proteoglycans
What do GAGs do and what is their structure?
Provide a hydrate gel to resist compressive forces - polysaccharides composed of linear repeated disaccharide units and make up proteoglycans - GAGs are linked to core proteoglycan by linker proteins (GAG portion looks like bottle brushes off of backbone)
What gives proteoglycans their biological functions?
THe GAG chain and their linker proteins present with different protein ligands give different roles like coagulation, lipolysis, inflammation, etc.
Which type of GAG is non-sulfated?
Hyaluronic acid?
Where is hyaluronan found and what is it’s role?
Skin, umbilical cord, eye, synovial fluid of joints, gives lubricating and resistance to compression rles
What are some external uses of HA?
Lubrication for eye surgery, tumor marker for progression of breast and prostate cancer, wound healing scaffolding, reduce pain in osteoarthritis by lubrication, anti adhesive product, and fillers in ccosmetic applications
What gives ECM tensile strength and elasticity?
Fibrous protein - adhesive glycoproteins
What is the major fibrous protein in the ECM? and what do they do?
Collagen - give tensile strength and structural support
Where is Collagen I found and how abundant is it?
Skin, tendon, vasculatures, organs, BONE - most abundant >90%
Where is Collagen II found?
Cartilage
Where is Collagen III found?
Reticulin - reticular fibers or blood vessels
Where is Collagen IV found?
Forms bases of cell basement membrane
What do most collagen related diseases arise from?
Genetic defects or nutritional deficiencies
What does degradation of collagen lead to?
Wrinkles
What is osteoporosis?
Not inherited genetically, brought on with age and gender (estrogen deficiency) - reduced levels of collagen in skin and bones
What is osteogenesis imperfecta and what causes it?
Cause by a mutation in collagen type I in bone causes fragile bones - can also give scoliosis
What is chondrodysplasias?
A skeletal disorder caused by a mutation in type 2 collagen (cartilage) - defect in development of cartilage of long bones giving arrested growth and dwarfism
What can help decrease swelling in Rheumatoid arthritis patients?
Organ administration of type II collagen
What is the structure of collagen?
A triple alpha helix forms a tropocollogen molecule and these line up to give fibrils
What are some medical applications of collagen?
Bone grafting as triple helix makes it strong and does not compromise skeletal structural integrity and is prevented from enzyme breakdown - scaffolds for tissue regeneration and deposition of cells - skin grafts - wound healing processes and cosmetic fillers
What do elastins do?
Give elasticity to tissues allowing them to stretch and return to their original pposition
Where are elastins found?
Blood vessels, lungs, skin, bladder, ligaments, elastic cartilage
What are elastins synthesized by? What degrades them?
Fibroblasts and smooth muscle cells, elastase enzymes degrades activated by fibroblasts and inflammatory cells and MMPs also degrade
What are the elastin receptors?
Fibulin-5, Elastonectin, Ficolin, Hucolin
What are some diseases associated with elastin?
Some congenital heart defects and hypertension, elastolysis (cutis laxa is the absence of elastin fibers - rare and inherited gives loose folds), williams syndrome, menkes, Marfan’s syndrome, and hurler disease
How much can elastin stretch and why?
1.5 times their length and snap back to original length because of heavy crosslinking
What are examples of adhesive glycoproteins?
Fibronectin, laminin
What is the structure of fibronectin? and what is it’s cell binding sequence?
Rod like structure with three modules, tripeptide arg-gly-asp are the rgd cell binding sequence - binds to integrin receptors - exists as a dimer in its active form consisting of two nearly identical monomers linked by disulfide bonds
How are fibronectins secreted and where do they bind?
Secreted in unfolded, inactive form and then bind to integrins which unfold the fibronectin molecules - where they can form dimers
Do fibronectins bind substances besides integrins?
Yes, they are multiadhesive
What are two types of fibronectins present in vertebrates?
Insoluble cellular FN - secreted by fibroblasts, major ECM component
Soluble plasma FN is a component of blood plasma produced in liver by hepatocytes
What is the function of fibronectin?
Cell adhesion, growth, migration and diifferentiation in cell signaling, form blood clots in plasma, structural support and compartmentalization in cellular FN, embryonic development, carcinoma development - alters cell motility so cells get where they don’t belong, wound healing
What is required for collagen to deposited at wound sites?
FN
What are laminins? What is their structure?
A family of glycoproteins that are import to the structural scaffold - major proteins of basal lamina - a heterotrimeric multi-adhesive matrix protein - from networks of web-like structures that resist tensile forces - vital for maintenance and survival of tissues, cell differentiation, migration and adhesion - t structure is advantageous to cross linking
What do laminins bind?
Other ECM components like collagens
What diseases result from laminin issues?
Congenital muscular dystrophy gives weak muscle, joints and retardation and junctional epidermolysis bullosa (JEB) a skin blistering disease, breast cancer development, neural development - substrate for nerve axon growth
