The Connective Tissues Flashcards
Simple columnar epithelia/Pseudostratfield
Elongated cells-including mucus-secreting cells and absorptive cells (lining of small intestine)
Micro villi-on apical surface
Favours max surface of absorption/secretion
Simple squamous epithelia
Thin cells-including cells lining blood vessels (endothelial cells/endothelium) and many body cavities .
Favours gas and molecules exchange
Transitional epithelia
Several layers of cells with different shapes-lining certain cavities (urinary bladder)
Favouring expansion and contraction (elasticity)
Stratified squamous
Line surfaces such as mouth and vagina
Resist abrasion & favours protection
Animal tissues
Epithilea
Connective
Muscular
Neuronal
Blood
Epithelia
Adhesion structures
Adhesion molecules
Connective tissues
Loose and dense
Hold organs together
Low in cells and high in collagens,reticular and elastin fibres
Specialised :adipose,cartilage,blood,lymph
Extra cellular matrix
Basal lamina
Connective tissues
-loose and dense
How
Functions of the extracellular matrix
1-Anchoring &surrounding cells to maintain solid tissue3d architecture and define tissue boundaries ,connects epithelial to basal structure
Heterogeneous family of integrins from basal side of epithelia bind to fibronectins,elastins and collagen
FOEM
Determining the biomechanical properties(stiffness/elasticity,porosity,shape) of the extracellular environment
FOEM-3
Controlling cellular polarity,survival,proliferation,differentiation and fate(e.g-asymmetric division of stem cells)&this embryonic and neonatal development and adult function and response to environment and disease
FOEM-4
Inhibiting or facilitating cell migration (e.g-serving as either a carrier to movement or conversely,as a ‘track’ along which cells -or portions of cells -can move
FOEM-5
Binding to & acting as a reservoir of growth factors ;in some cases ,the ECM
1-helps generate an extra cellular concentration gradient of the growth factor
2-serves as a co-receptor for the growth factor
3-aids in proper binding of the growth factor to its receptor (ECM component and growth factor jointly serve as a receptors combined ligand)
FOEM-6
Activating cell surface signalling receptors
How is th extracellular matrix
Formed by basal lamina and underlying connective tissues
ECM componanats
Proteoglycans
Collagens & Elastin
Multi-adhesive matrix proteins
What are proteoglycans ?
A unique type of glycoproteins,hydration and mechanic protections
What do collagen and elastin do ?
Form fibres and give elasticity
What are multiadhesive matrix proteins?
Important organisers of the extra cellular matrix
Fibronin and laminin
-long,flexible molecules that contain multiple domains
-bind various types of collagen other matrix proteins,polysaccharides and extracellular signalling -molecules as well as adhesion receptors
:Regulate cell matrix adhesion and cell shape and behaviour
What is the Laminin molecule ?
Heterotrimeric multi-adhesive matrix protein found in all basal laminate
-16 vertebrae laminin isoforms -assembled from 5a,3b &3y chains
-coiled-coil regions-3 peptides covalently linked by several disulfide bonds
-Globular domains-bind to/crosslink adhesion receptors and various matrix components
-5 a subunits C-terminal globular LG domains -mediate Ca2+ dependent binding to cell surface laminin receptors including certain integrins (hemi desmosome),sulfated glycolipids,syndecan,and dystroglycan
-inset: laminins assemble into a lattice via interactions between their N-terminal globular domains
Structure of Laminin molecule
-Charectireristic cross-shape
Carbohydrate -binding LG domains near the C-terminus
Structure & assembally of type 4 collagen
Sheet-forming type IV collagen is a major structural component of the basal lamina
a
-400 nm long molecule
-N-terminus - small globular domain
-C-terminus-large globular domain
-collageneous triple helix -interrupted by nonhelical segments that introduce flexible kinks into the molecule
Formation of diners,tetramers,& higher order sheet -like networks ?
-lateral interactions between triple-helical segments
-head-to-head and tail-to-tail interactions between the globular domains
-multiple,unusual sulfilimine (-S=N-) or thioesther bonds between hydroxylysine (or lysine) & methionine residues covalently cross-link some adjacent C-terminal domains and contribute to the stability of the network
Type IV collagen network formed in vitro (EM) ?
-Side to side triple helical segment binding
C-terminal globular domain interactions
Extra-cellular matrix and connective tissues
-Connectve tissues are diverse depending on the organs
-the ration between cells & ECM components ,varies greatly
-connnective tissue including tendons and cartilage is mostly ECM
Fibres dense and cell scares (chondrocytes,fibroblasts,lymphocytes,endothelial cells)
Main molecular component of ECM of connective tissue ?1
Collagens-from Latin colla are trimeric molecules that are often bundled together into fibres( fibrillar collagen);very abundant in all connective tissues & very heterogenous
Main molecular component of ECM of connective tissue ? 2
Proteoglycans : glycoproteins containing one or more covalently bonding GAG chains .Play an important role in cell-matrix adhesion.They can be cell-surface linked (Perlecans) or secreted in extra-cellular space
Main molecular component of ECM of connective tissue ?3
Glycosaminoglycans (GAGS) specialised linear polysaccharides chains of specific repeating disaccharides ,negatively charged ,that can be highly hydrated and confer diverse binding and physical properties (e.g: resistance to compression :ie hyaluronate)
Main molecular component of ECM of connective tissue ? 4
Multi-adhesive proteins large multi domain proteins often compromising many copies (repeats) of a few distinctive domains that bind to and crosslink a variety of adhesion receptors and ECM compants
Main molecular component of ECM of connective tissue ?5
Elastin a rubber like protein that forms the amorphous core of elastic fibres ,typically high in organs that stretch like the heart ,tendons ,vessels ,bladder and skins
Most compacts are produced and re modelled by resident fibroblasts
Types of callogens ?
collagen
Trimeric protein made of 3 polypeptide -can be identical (homotrimer) or different (heterotrimer)
Peptides- encoded by one of at least human 43 collagen a chain genes
Structure of collagen
LONGITUDINAL
Polypeptide fragment -contains repeating sets of Gly-X-Y amino acids characteristic of collagen a chains
-each chain is twisted into a left handed helix -3 chains wrap around one another in a right handed triple helix
-triple-helical structure with left handed twist of the individual collagen a chain
COLLAGEN STRUCTURE 2 -
Cross sectional view
Glycine proton side chains-located in the very narrow space between the polypeptide chains in the center of triple helix
Collagen glycine mutations -larger R group disrupt trimer chain packing of the chains—destabilise the triple-helical structure
Proteoglycans (PG)
Subset of secreted and cell surface (perlecans & sydecans in basal lamina) glycoproteins containing covalently linked GAG
- GAG are linear polymers of repeating disaccharides
- Generally glucuronic & ioduronic /galactose linked to N-acetyl-glucosamine/galactosamine
-PG are produced by cells with the protein core produced in RER and GAG assembled in the Golgi before secretion (O-linked oligosaccharides)
Proteoglycans 2
Mucin glycoproteins on surface of epithelia help -curvature of cells aka form microvilli
Others bind to cadherins to stabilise the cell-matrix interaction
Heparan sulphate controlling the blot clotting cascade
Hyaluronic acid
Hyaluronon is a non-suphated GAG made by plasma membrane bound enzyme called HA synthase
-secreted directly into extracellular space as its synthesised
Resists compression ,fascilliates cell migration ,and provides cartlidge its gel-like properties
-surrounds migrating &proliferating cells -embryonic
-forms background of complex proteoglycans aggregates found in many ECMs including cartlidge
Some HA molecules range to 10 micrometers
Fibronectins
Fibroblasts expressing fibronectins on their surface adhere to Petri dishes
-cancer cells-lose expressions,detach and float
-20 isoforms
-pave route for embryogenesis &differentiation
-essential in healing process-regulate clotting&lead way for macrophages
Tissue modelling & remodelling
ECM needs to to be responsive to changes in the environment -moving in cells,during inflammation,
Metalloproteases are secreted by fibroblasts and tissues like elastases ,collagenenases and help breaking down the ECM network to fascillitate cell movement in physiology &pathology
-Secretion or activation in response to stimuli-growing factors / cytokines
Tissue modelling & remodelling
Fibroblasts are most common cell type
Central mediators of pathological fibrotic accumulation of ECM & cellular proliferation and differentiation that occurs inn response to prolonged tissue injury and chronic inflammation
Tissue modelling & remodelling
Fibroblasts sensitive to signals like cytokines,chemokines and growth factors which instruct to manipulate ECM fibres physically close open wounds
, fibroblasts have multiple concomitant biological roles, such as in wound healing, inflammation, and angiogenesis, which are each interwoven with the process of fibrosis.
many common fibroblast-related features across physiological and pathological role of non-cancerous fibroblast interactions with tumors in cancer progression.
