Adhesion Flashcards
fuctional types of cell junctions
- anchoring: mechanical attachment to other cells or ECM
- occluding: seal contacts b/t neighboring cells
- channel-forming/communicating: form channels b/t cells and allow chemical and electrical signals to pass
junction structure
-transmembrane adhesion receptor proteins contact inside and outside environments
-extracellular region attaches to other adhesion proteins or ECM molecules
-intracellular regions attach to cytoplasmic adaptor proteins and connect to cytoskeletal linkers or cytoskeletal proteins
adapter proteins bind adhesion complex and recruit additional regulatory components
what increases junciton stability and strength?
- they are multiprotein complexes
- clustering of adhesion proteins inc. stregth
- clusters link to cytoskeletal network producing a large tension bearing network through tissue
cell polarity
- regional differences w/in cell
1. apical domain-free, unattached PM facing open space, may be air or fluid filled
2. lateral domain-contacts neighboring cells
3. basal domain-attached to ECM, often faces underlying connective tissue
tight junctions/zonula occludens
zonula=belt around cell
located apically and join neighboring cells
-formed by strands of transmembrane proteins-mainly claudin and occludin (occludins required for barrier function)
-control diffusion of material b/t cells
adherens junctions/zonula adherens
form cont. belts around cell on the lateral domain just under tight junctions
- important for sheet formation of epithelial cells
- made of classical cadherins
1. at low Ca levels two cadherins form a cis-homodimer
2. Ca binding causes a confrormational change and straightens cadherins, which promotes trans-homodimer formation and facilitates binding to neighboring cells
3. cadherins cluster and link to cytoskeleton via catenins
desmosomes/macula adherens
small, spotlike junctions that strengthen adhesion b/t epithelial cells exposed to tensile forces/mechical stress
-based on adhesions b/t cadherin-like receptors desmocollin and desmoglein which bind to intermediate keratin filaments
gap junctions
- allow communication and sharing of small molecules b/t neighboring cells
- connexins (6) cluster together and make connexon, which binds connexons in similar cells, which forms a channel
connective tissue ECM
composed of ground substance and fibers
ground substance
-water, electrolytes, polysaccharides and proteins, resists compression and allows diffusion
main components
1. glycosaminoglycans-chains of carbs that are negativly charged and attract Na and water
2. proteoglycan-many long GAGs linked to a protein
3. glycoproteins-proteins w/short carb chains added-1-60% carb
fibers
collagen-main ECM protein that is flexible but strong and not stretchy
-made up of units of tropocollagen (which is a helex of 3 alpha collagen protein subunits)
elastin=stretchy and distensable
other connective tissue components
- fibroblasts: cells that synthesize ECM components
- specialized connective tissues contain osteoblasts, chondroblasts, and adipocytes
basement membrane
specialized ECM that forms carpet like mechanical barrier b/t epithelial and connective tissues and anchoring point for epithelial cells that attach via hemidesmosomes
-consists of basal lamina and reticular lamina
basal lamina
- lamina lucida-laminin glycoproteins and integrins-clear portion on TEM
- lamina densa-mostly type IV collagen, gives tensile strength, dark on TEM
- laminin binds collagen and links two layers
reticular lamina
contains type I and III collagen and fibrillin
binds anchoring plaques, fixing basement membrane to connective tissue ECM
integrins
- transmembrane ECM binding protein receptors
- heterodimers of alpha and beta subunits (many combinations of different alpha and beta)
- exist in high and low affinity states
intigrin activation
- outside in-binding of ECM ligands
2. inside out-integrin binds proteins that shifts their affinity state
focal contacts
- link to actin, many cell types
- receptor is one of many integrin heterodimers
- dynamic, can generate traction forces–>important in cell movement
- critical for mm attachment to tendons
hemidesmosomes
- link to intermediate filaments, found in epithelial cells only
- alpha6beta4 integrin heterodimer
- bind basal surface of epithelial cells to laminin of underlying lamina lucida
epithelium
- cont layers of cells with very little ECM
- cells adhere to basemembrane via hemisesmosomes
- acts as protective covering
- regulates transport by 1. paracellular transport (where tight junctions are not occluding and 2. transcellular where tight junctions are occulding
- regulates absorbtion
- regulates secretion
1. exocrine from apical side onto free surfaces and ducts
2. paracrine from basal side into underlying connective tissue
3. endocrine from basal side into underlying connective tissue-product enters bloodstream
Connective tissue
- structural support, medium for exchange, storage of lipids
- from mesoderm
- consists of cells and ECM (ground substance and fibers)
- is vascularized
connective tissue cell types
- come from mesenchymal stem cells or pleuripotent hemopoetic stem cells
- fibroblasts make ECM
- adipocytes-store lipid droplets in cytoplasm
- pericytes-pleuripotent mesenchymal stem cells associated with blood vessels of CT that can become adipocytes, fibroblasts, or endothelial cells
connective tissue proper classifications
- loose/areolar-many cells, lots of ground substance, few fibers, flexible and not stress resistant
- dense irregular-few cells/more fibers, in all orientations, resistant to stress in all directions
- dense regular-fibers parallel and strength in one direction
- adipose CT-high number of adipocytes grouped into lobules separated by dense CT–septae
- reticular CT-highly cellular w/interwoven reticular fibers
glands
- secretory epithelial portion-parenchyma
- CT inductive and supportive
types of glands
- unicellular-single cells in surface, eg goblet cells
- multicellular glands-clusters of secretory cells surrounded by stroma, secrete into duct, eg salivary glands
- simple=unbranched, compound=branched
- morphology: tubular=same diameter as duct, alveolar=expanded diameter
cartilage functions
- supports soft tissues
- provides low friction sliding for joints
- growth of long bones as reserve for new bone deposition
cartilage cells
chondroblasts deposit cartilage ECM and arise from chondroprogenitor cells in perichondrium
chondrocytes in lacunae
cartilage matrix
resists compression, intermediate thickness collagen type II fibers for tensile strength
avascular and relies on high diffusion and hydration
hyaline cartiage
type II collagen fibers, significant amounts of proteoglycans
- well defined perichondrium, limited regenerative potential
- found in joints, nose, trachea
fibrocartilage
- thick, strong, collagen type I for highest tensile strength
- no distinct perichondrium very very low regenerative potential
- intervertebral disks, sites of tendon attachment, some joints
- eventually degenerates and can be replaced by bone
elastic cartilage
- less matrix and more cells than hyaline
- type II collagen and elastic fibers
- well defined perichondrium, limited regenerative potential
- found in flexible areas like ear, epiglottis
osteoarthritis
degenerative loss of hyaline cartilage
in joints, bone contacts bone
osteoblasts
osteocytes
deposit osteoid (organic ECM) trapped in lacunae (inorganic mineralized part), make caniliculi for communication
osteoclasts
only bone cells derived from hematopoetic stem cells
-resorb/breakdown bone matrix
periosteum
outer fibrous layer and inner cambium layer (osteoprogenitor cells), attached to bone via sharpys fibers
inner spongy bone
small spikes/trabiculae that contact bone marrow
-remodeled by osteoclasts, lacunae filled in by osteoid deposited by osteoblasts
outer compact/cortical bone
made of osteons of concentric layers that form haversian canal in middle
bone formation
- intermembranous (flat bones): forms in mesenchyme, which condeses and generates osteoprogenitor cells that differentiate and lay down bone matrix
- endochondrial-ossification centers form where cartilage makes scaffold that is then replaced with bone
1. central ossification center=diaphysis, outer ones are epiphyses
2. epiphyseal plate gradually ossifies and becomes bone in response to growth hormone
osteoporosis
shift toward resorption of bone ECM
-inhibit osteoclasts with bisphosphonates (which mimic hydroxyapatite and prevent the breakdown of actual hydroxyapetite)
botox
prevents release of ACh from axon terminals by inhibiting fusion of vesicles to pre-synaptic membrane of NMJ
Muscular distrophy
- loss of cytoskeletal linker protein dystrophin causes ECM junction to be released from actin cytoskeleton
- results in contraction injuries, followed by inc in connective and adipose tissue that initially causes pseudohypertrophy in the calf muscle
cardiac myofibers
- mononuclear, centrally located
- branched and connected by intercalated disks
intercalated disks
adhesion junctions-anchor myofilaments (terminal sarcomeres) to actin cytoskeleton
desmosomes anchor adjacent cardiomyofibers
gap junctions (parallel to myofilaments) allow rapid info flow b/t fibers
cardiac muscle contration
- diad instead of triad (one cistern) releases small amounts of Ca, T-tubules facillatate extracellular Ca transfer to sarcoplasm
- intercalated disks allow for quick passage of ions b/t fibers
- cardiac muscle has sarcomeres
smooth muscle fibers
- spindle shaped, tapered, one nucleus
- no sarcomeres, actin and myosin filaments attach to dense bodies and dense plaques at PM
contraction of smooth muscle
no t-tubule based contraction, instead is large number of gap junctions to allow direct electrical communication b/t fibers
contractile units consist of myosin and actin filaments