Extracellular matrix/histology Flashcards
interstitial fluid
A complex aqueous soup of ions, proteins, proteoglycans, and signaling molecules that surrounds normal cells.
Extracellular Matrix
Composed of interstitial fluid and all surround matrix that make up the surrounding environment. Contains fibrous proteins and proteoglycans.
Extracellular function
provides shape/structure to interstitial space, lubrication and cushioning, provides anchor point for cell adhesion, allows communication between cells and controls life cycle.
ECM protein that provide structure and attachment
Collagen fibers, elastin, fibronectin
ECM that prevent compression?
GAG’s such as hyaluronic acid, chondronitin sulfate, dermatin sulfate, heparan sulfate, keratin sulfate.
Collagen
Major protein of ECM and 30% of protein mass in body. Many different collagen that differ in function, distribution, and organization. Two types: Fibrillar and nonfibrillar.
Collagen structure.
Each protein has unique left-handed helix with three amino acids per turn (Gly-X-Y) glycine, proline, hydroxyproline. Glycine compose the middle of protein and proline/hydroxyproline are on the outside that provide support.
Tropocollagen
three helical collagen proteins come together to make a triple-stranded right-handed super-helical Quaternary structure.
Fibrillar Collagen
Formed from mixture of collagen types that provides tensile strength to skin, tendons, and ligaments. Long overlapping of tropocollagen
Non-fibrillar collagen
Basement membrane collagen (type 4). Has interrupted tropocollagen. Interacts with fibrillar to form mesh-like structures.
Basement membrane
Thin layer of ECM of type 4 collagen that surrounds tissues to create barrier. Main purpose is to prevent migration of certain cell types.
collagen Synthesis
Preprocollagen is synthesized with a signal directing it to the lumen of the ER. Removal of signal results in procollagen. Post-transnational modification in the ER (proline converstion, attach sugar to protein, disulfide bonds incorporated). Disulfide bond formation triggers triple helical formation (tropocollagen). Transported to golgi and exocytosed. Converted to mature collagen by proteolysis and then can crosslink to form insoluble collagen.
Scurvy
Vitamin C deficiency via collagen synthesis.. VitC is a cofactor of hydrolase enzyme that produce hydroxyproline from proline.
Hydroxylase
convert proline to hydroxyproline in collagen synthesis. Occurs in ER.
Glycosylation
Attaches sugars to procollagen in ER.
Osteogenesis Imperfecta (brittle bone)
Point mutation in genes coding for alpha 1 or alpha 2 collagen chains. Changed amino acid sequence prevents formation of helical structure.
Elastin
Forms elastic fibers in blood vessels, lungs, ligaments, and skin. Single protein and has little post-translational modification.
Desmosine
Elastin monomers cross linked to form two dimensional latticework allowing for stretching in two dimensions.
Fibronectin
ECM protein that is attachment point for other cellular and ECM components. Many isoforms that are both tissue and developmental specific. Involved in cell adhesion, migration, embryonic morphogenesis, and cytoskeletal/ECM organization.
Proteoglycans
Gel-forming portion of the ECM sometimes known as ground substance. Contains protein chains with large amount of complex carbohydrates called glycosaminoglycan (GAG). Main role to provide support to tissue ( cartilage and connective tissue). Prevent compression stress due to large negative charge.
Glycosaminoglycan (GAG)
May contain up to 100 sugars per chain with specific repeating sequences composed of uronic acid and amino sugar. They are polyanionic due to uronic acid and high levels of sulfation on the amino sugars.
Major proteoglycans of EMC
Hyaluronic acid, Chondroitin sulfate, Dermatan sulfate, Heparan sulfate, Keratan sulfate…..all are GAG’s.
Where are proteoglycan constructed?
In the golgi apparatus. Receives protein core from ER.
mucopolysaccharidosis
Disruption of degradation and synthesis at the point of the many enzymes involved in the processes.
