Extracellular Matrix Flashcards
What is the extracellular matrix?
Extracellular matrix is a complex network of polysaccharides and proteins secreted by cells for strengthening tissues.
made from:
(1) glycosaminoglycans (GAGs) which are large and highly charged polysaccharides that are usually covalently linked to protein in the form of proteoglycans
(2) fibrous proteins which are primarily members of the collagen family; and
(3) a large class of noncollagen glycoproteins, which carry conventional asparagine-linked oligosaccharides
Describe epithelial sheets/tissues
Epithelial Sheets/Tissues
- transfers molecules in/out and cells
- has receptors for environmental signals
- has less ECM than connective tissue
different types: simple, columnar, squamous, cuboidal, stratified
→ simple - found in mucus secreting cells, stomach lining
→ stratified - in mouth - resist abrasion
Epithelial sheets are polarised - differences between top and bottom
- apical - expanded by microvilli
- basal - rest on connective tissue, supported by basal lamina
What is the basal lamina?
Basal Lamina is a thin mesh of of extracellular matrix molecules secreted by the epithelial cells, on which the epithelium sits.
- fibrous network of collagen supports epithelial, connects with connective tissue - In the skin, for example, the epithelial outer layer—the epidermis—depends on the strength of the basal lamina to keep it attached to the underlying connective tissue—the dermis.
- composed of type IV collagen forms a 2D network, underpins the structural integrity of basal lamina and accounts for its mechanical strength
- contains multi-adhesive matrix proteins - e.g laminin (links integrins in plasma membrane of epithelial cells to connective tissue)
- perlecan (proteoglycan) has lots of different diverse binding partners - important for cross linking different components of basal lamina
→ important in tissue repair and development
- > surrounds individual muscle cells, fat cells, and Schwann cells
- > The basal lamina thus separates these cells and epithelia from the underlying or surrounding connective tissue and forms the mechanical connection between them
What are cell to cell junctions?
Cell to Cell Junctions
- found in plasma membrane between adjacent cells
- helps cell-cell communication
- separates apical and basal surface as chemical environments differ
Types:
Connects 2 cells
- Tight Junction
- Adheren Junctions
- Desmosome
- Gap junction
Connects cell and ECM
- Hemidesmosome
What are tight junctions?
Tight Junctions - Cell to Cell
- cells are held tightly against each other by many individual groups of tight junction proteins called claudins each of which interacts with a partner group on the opposite cell membrane. The groups are arranged into strands that form a branching network, with larger numbers of strands making for a tighter seal
- seals neighbouring cells together in an epithelial sheet to prevent leakage of molecules between them
- Barrier for the diffusion of membrane proteins and lipids
- form a seal (though not absolute)
- Calcium required for integrity of seal - can be broken down/dismantled depending on presence of calcium
→ form a branched network of sealed strands
→ each strand is an independent barrier to ion flow
→ permeability varies in different epithelia (small intestine epithelia 10,000x more permeable than urinary bladder)
What are gap junctions?
Gap Junctions - BETWEEN 2 CELLS or CELL to ECM
- forms small channels that allow small water soluble molecules, including ions, to pass from cell to cell
- Separates apical/basal surfaces
- cell junction filled with ion channels - permeability varies in different types of cells-
- high Ca2+ conc → channels close
→ connexons form hexagonal molecule that stacks on each other
→ each channel comprised of 12 connexon molecules
- Gap junctions have a pore size of about 1.4 nm, which allows the exchange of inorganic ions and other small water-soluble molecules, but not of macromolecules such as proteins or nucleic acids
Gap junctions in different tissues can have different properties because they are formed from different combinations of connexins, creating channels that differ in permeability and regulation.
In plants: Plasmodesmata
- are microscopic channels which traverse cell walls of plant cells and some algal cells
- enable transport and communication between cells
- enable direct, regulated, symplastic transport of substances between cells
What are adheren junctions?
Adheren Junctions are anchoring junctions - CELL TO CELL
- Use CADHERIN as transmembrane linker
- connected to actin filaments; joins an actin bundle in one cell to a similar bundle in neighbouring cell
→ adhesion proteins:
- Cadherins = transmembrane proteins whose
- extracellular segments bind to each other and
- whose intracellular segments bind to..
- extracellular segments bind to each other and
- β- catenin - are connected to actin filaments
- important in folding epithelial tissue and forming tubes → important in neuronal development
- important in controlling cell shape - in epithelial tissue, belt of actin and myosin filament rings the inner surface of cell adjacent to the adheren junctions, where cell-cell contacts maintained. The circumferential belt is attached by linker proteins to cell-adhesion molecules in plasma membrane
What are desmosomes?
Desmosomes are anchoring junctions - CELL TO CELL
- Use CADHERIN as transmembrane linker
- connected to INTERMEDIATE FILAMENTS
- provide mechanical strength
- distribute sheering forces across epithelial sheets
- Cadherins connect cells by binding to desmoplakin which binds to intermediate filaments
What are hemidesmosomes?
Hemidesmosomes are anchoring junctions - CELL TO ECM
- Use INTEGRIN as transmembrane linker
- Connected to INTERMEDIATE FILAMENTS
- anchors intermediate filaments in a cell to basal lamina
- anchor intermediate filaments and distribute sheering forces
- integrins mediate adhesion forces to laminin
Describe cell adhesion molecules (CAM) and their regulation
Cell Adhesion Molecules (CAM) are a subset of cell adhesion proteins located on the cell surface Involved in binding with other cells or with the extracellular matrix (ECM) in the process called cell adhesion
- help cells stick to each other and to their surroundings
- essential for cell-cell communication
- disruption in cell-cell interactions → devastating effects on embryo development, cancer, metastasis
e.g
→ Cadherins
- found at adheren junctions
- specialised cadherins with different intracellular domains found at desmosomes
→ Integrins
- found at hemidesmosomes
Regulation of CAMS:
- Proliferation
- Migration
- Differentiation
Describe Cadherin dependent adhesion
Cadherins are a type of cell adhesion molecule (CAM)
- concentrated at adheren junctions
- desmosomes - have specialised cadherin proteins with specialised intracellular domains
Interaction of cadherins with other cadherins is calcium dependent
→ calcium rigidifies cadherin oligomers → allows cadherins to interact more strongly
→ strength of reaction comes from avidity → collective reactions are strong, individual are weak
→ through avidity, you can propagate signals through tight adhesion molecules
Cadherins bind to adaptor proteins through intracellular domains like actin cytoskeleton (binds to B-catenin which binds to cadherins)
At desmosomes, cadherins have different adaptors that connect to intermediate filaments
- Packing of individual molecules into a crystal - useful as it mimics high localised concentration that is observed at adheren junctions
- interactions across molecules gives insight with how an individual cadherin interacts with another on cis
Describe integrin dependent adhesion
Integrins are a type of CAMs that mediate cell adhesion to the ECM
found at hemidesmosomes
- bridge between ECM by binding to collagen and cytoskeleton via adapters
→ cluster to have an avidity effect on interaction faces
→ composed of heterodimers: α and β subunits
→ 18 different types of α integrin, 8 different types of β integrin → can have lots of different combinations to bind to lots of different ligands
How do integrins work as signalling molecules?
- transport signals inside cell and outside cell
- they do this by transmitting different conformational changes in protein structure
- level of adhesion affected by expression level of integrin on cell surface
Active = cytoplasmic tails brought apart
Describe the connective tissue
- abundant environment that cells live in
- varied in form - e.g tough and flexible (tendon), hard and dense (bone), shock absorbing (cartilage), soft (jelly in eye)
- tensile strength provided by fibrous protein - collagen (produced by fibroblasts)
- various types of connective tissue depend on type of collagen
Describe collagen and its organisation
Collagen
- single polypeptide chain winds into triple stranded helical structures
- rich in proline and glycine (properties affect structure and rigidity)
- exit cells via exocytosis - via vesicular trafficking pathways (big cargo)
- fibroblasts - connective tissue in skin
- osteoblasts - connective tissue in bone
- gram for gram, collagen is stronger than steel
- resist stretching forces that happen in connective tissue
What are the roles of fibronectin and integrin?
Fibronectin binds to collagen and integrin
→ fibronectin and integrin help attach cytoskeleton network to ECM
- cells do not attach well to collagen directly - collagen binds to fibronectin which binds to integrin dimers which binds to actin skeleton
- important role in migration and cell differentiation
