ECM And Cell Adhesion Flashcards
Does CT or epithelial tissue have more ECM and less cells?
CT, epithelium is opposite
GAGs and relation to water
. Repeating disaccharide units w/ negative charges ( acidic sugar and N-acetylated amino sugar)
. H2) floods into ECM w/ GAGs bc of neg. charge causing swelling pressure (turgor) allowing ECM to resist tissue compression forces
Formation of proteoglycan monomers
. Core protein w/ GAGs covalently bonding extending out from it
What do individual proteoglycan monomers associate w/?
Hyaluronic acid
Percentage of protein mass made up of collagen?
25%
Collagen fiber structure
. Collagen molecules made up of 3 chains (alpha chains) that wind around each other
. Every 3rd amino acid is Gly allowing tight packing
. Packaging of collagen molecules w/in fibrils leads to repeating structure w/ a banding pattern
Synthesis of collagen
. Individual collagen polypeptide chains are translated on membrane-bound ribosomes
. Selected Pro and Lys hydroxylated (dependent on Vit. D)
. Some hydroxylysine residues are glycosylated
. Triple helix forms
. Excreted into ECM and propeptides cleaved to yield tropocollagen
. Mature collagen formed from cross linking of tropocollagen
Cross-linking of collagen fibrils
.allysyl residues formed on fibrillar array acted on by lysyl oxidase allowing them to form covalent cross links seen in mature collagen fibers
Cross linking function
Tensile strength for proper functioning CT
Elastin structure
. Has small, nonpolar amino acid residues (Gly, Ala, Val)
. Rich in Pro and Lys but little hydroxyproline and NO hydroxylysine
. not glycoprotein
. Not triple helical
. Some side chains of Lys modified to form allysine
. 3 allysine residues and side chain of 1 unaltered Lys joint together covalently to form desmosine cross link
Elastin modifications once excreted into ECM
. Tropoelastin (new elastin in ECM) interacts w/ glycoprotein microfibrils (fibrillin) that serve as scaffolding onto which tropoelastin is deposited
. Side chains of Lys residues of tropoelastin modified to form allysine residues
. 3 alysyl residues and side chain of 1 unaltered Lys residue joined together covalently to form desmosine cross link
Where are fibronectin and laminin found?
Fibronectin: CT
Laminin: epithelial tissues
Binding domains of fibronectin and laminin
Cell, collagen, and proteoglycans
How are many simple tissues derived from?
precursor cells whose progeny are prevented from wandering away by being attached to ECM, other cells, or both
What is selective adhesion essential for?
.development of tissues that have complex origins involving migration
Cell junctions
. Occluding (tight): form physical barrier
. Anchoring (desmosome): couple neighboring cells to each other or to ECM through interactions mediated by cytoskeleton
. Communicating (gap): attach cells to allow signal transfer
Families of adhesion molecules
. Cadherin
. Selectins
. Immunoglobulin superfamily
. Integrin
Cadherins
. Mediate Ca-dependent cell-cell adhesion by homophilic mechanism
. Transmembrane linker proteins that mediate interactions btw actin of the cytoskeleton of the cells they join together
. Play role in holding cells and maintaining tissue integrity
Selectins
. Cell-surface-carbohydrate-binding proteins that mediate heterophilic binding
. Function in transient cell-cell adhesion interactions, important in bloodstream
. Enables WBCs to bind endothelial cells and migrate to sites of inflammation
Immunoglobulin Superfamily
. Mediate Ca-independence cell-cell adhesion by homophilic or heterophilic binding
. Transient expression during development implicating a role for these ,ole clues in development
. Cell-cell adhesion mediated is weaker than adhesion by cadherins
. Contribute to regulation or fine-tuning of adhesive interactions during development and regeneration
Integrin
. Adhesion molecules consisting of alpha and beta transmembrane chains important for cell-matrix and cell-cell adhesion
. Beta 2 type of beta subunit expressed only on leukocytes to participate in cell-cell interactions through integrin binding to other adhesion molecules on other cells
. Mediate bidirectional interactions btw cytoskeleton and ECM
. Most connect to bundles of actin
. Cytoplasmic portion interacts w/ cytoskeletal components and it important for transmission of signals btw inside and outside of cell
T/F integrins bind ligand with low affinity
T, attachment of cells to ECM depends on multiple weak adhesions
T/F Integrins with different alpha and beta chains have different binding properties
T
different alpha and beta chains
14 alpha
8 beta
Fatty streak
. 1st pathological changes in atherosclerosis
. Located on tunica intima
Process of extravasation
. Rolling
. Triggering
. Arrest/Firm adhesion
. Diapedesis
What is extravasation mediated by and how?
Adhesion molecules
. Monocytes binds to ligand (member of Ig superfamily) on surface of endothelial cell to roll
What is activated during cell triggering in extravasation
. Integrins on monocyte are activated and firm arrest monocyte
What follows stable arrest and what molecules are involved?
. Diapedesis
. Same integrins in arrest participate in trans endothelial migration in conjunction w/ other adhesion receptors
After diapedesis what steps occur in cardiovascular disease?
. Macrophages consume excess modified (oxidized) lipoprotein becoming foam cells
. Foam cells accumulate and release growth factors that stimulate proliferation of smooth muscle and calcification of plaque
Receptors on foam cell
. Low affinity non-specific scavenger receptors take up modified LDL (oxLDL)
. High affinity receptors specific for LDL becomes downregulated when cell has sufficient cholesterol
LDL to oxLDL reaction
. LDL oxidized w/ oxidants, Vit. E, beta-carotene, ascorbic acid to oxLDL
What can help w/ joint health?
Glucosamine
Where are individual fibrillar collagen polypeptide chains translated?
Membrane bound proteins (rER)
Tropocollagen
Collagen that is excreted into ECM before cross-linking
Scurvy
. Vit. C deficiency
. Lack of hydroxylation of Pro and Lys causing defective pro-alpha chains so you cannot form a stable triple helix and immediately degrade in cell
. Only new collagen is affected
Scurvy symptoms
. Blood vessels fragile . Bruising . Wound healing slows . Tooth loss occurs . Fractures can happen but not common in adults . Mimic child abuse signs in children
Osteogenesis Imperfecta
. Abnormal collagen type I production
. Most common type is type I where there’s low concentration of collagen of normal structure
. Type II is lethal
Mutation in Marian syndrome
. Fibrillin-1 (FBN1) causes alpha1-antitrypsin deficiency
. FBN1 defective causes inc. in TGF-beta)
Alpha-antitrypsin deficiency
. Normally keeps neutrophil elastase destruction in check to prevent damage to normal lung elastin
. W/ deficiency there is dec. inhibition and lung tissue cannot regenerate
Pemphigus
. Autoimmune blistering disease related to adhesion
. Autoantibodies develop against cadherins, disrupting their interactions
