cellular adhesion Flashcards
Importance of adhesion
Tissue formation
In order for tissue to be formed, early cells of similar type must come together to develop into a functional tissue
Different tissue forms due to a process explained by the Differential Cell Affinity hypothesis or Differential Adhesion hypothesis
What is this hypothesis?
Cells congregate near other similar cells with similar adhesion molecules to maximise the bonding (adhesion) strength between cells by creating a more thermodynamically stable (less energy costing) tissue or structure
Cell junctions- class of functional cell junctions
The differences in strength of cohesion between cells is caused by the types and numbers of adhesion molecules on expressed on cell surfaces
Four functional classes of cell junctions in animal tissues
Anchoring
Occluding
Channel-forming
Signal-relaying
Anchoring junctions
Anchoring junctions
Provide structure and strength to epithelial cells
Transmit stresses by pulling on the cytoskeleton
Some can stand higher stress on the tissue (e.g. connective tissue)
Two types: cell-to-cell and cell-to-matrix
Cell-to-cell: two structures
Adherens: connect actin filaments in one cell with that in the next
Desmosome: connect intermediate filaments in one cell with that in the next
Cell-to-matrix
Actin-linked cell-matrix: anchors actin filaments in cell to ECM
Hemidesmosome: anchors intermediate filaments in cell to ECM
Each of the major anchoring junctions depends on transmembrane adhesion proteins that span the plasma membrane
One end links to cytoskeleton and the other links to structures outside the cell
Two superfamilies of cytoskeleton-linked transmembrane proteins: cadherins, integrins
Occluding junctions
Tight junctions
Seal gaps between cells to make them impermeable e.g. BBB
Establishes polarity (apical/basal)
Prevent backflow from one side of the epithelial layer to the next
Channel-forming junctions
Gap junctions
Link cytoplasms of adjacent cells
Signal-relaying junctions
Synapses in nervous system
Anchoring junctions-Adherens junction and desmosomes
Composed of cadherins
Family of transmembrane proteins that form homodimers in a calcium-dependent manner with other cadherin molecules on adjacent cells
Cell adhesion is mediated by extracellular cadherin domains
Adherens: classical cadherin binds to classical cadherin on neighbouring cell via actin filaments
Desmosomes: non-classical cadherins desmoglein/desmocollin bind to similar molecule on neighbouring cell via intermediate filaments
Anchoring junctions-Actin-linked cell-matrix junctions and hemidesmosomes
Composed of integrins
Family of transmembrane proteins that form heterodimers
ALCM: integrin binds to ECM proteins (fibronectin) via actin filaments
Hemidesmosomes: a6b4 integrin binds to ECM proteins (laminin) via intermediate filaments
Homophilic
adhesion created by interaction between two similar adhesion molecules
Heterophilic
adhesion created by interaction between adhesion molecules and extracellular matrix proteins
Occluding junctions
Tight junctions
Epithelial cells are polarised
Basal side – anchored to tissue
Apical side – not attached
TJ maintain the polarity of cells by preventing the lateral diffusion of integral membrane proteins between theapicalandlateral/basalsurfaces
Allows the specialised functions of each surface to be preserved
Epithelia are selectively permeable barriers
Tight junctions seal gaps between cells to make them impermeable
Prevent the passage of molecules through the space between cells, so materials must enter the cells in order to pass through the tissue
Blood brain barrier, intestinal brush border
Tight junctions
TJ join together cytoskeletons of adjacent cells
They are composed of a branching network of sealing strands, each strand acting independently from the others
Each strand is formed from a row of transmembrane proteins embedded in both plasma membranes, with extracellular domains joining one another directly
The major proteins involved are theclaudinsand theoccludins
These associate with different membrane proteins such as ZO-1 located on the intracellular side of plasma membrane, which anchor the strands to the actincomponent of thecytoskeleton
The extracellular matrix
Many different proteins and polysaccharides
Relative amounts of components can be altered giving rise to a wide diversity of materials
Calcified – bone, teeth
Transparent – cornea
Rope-like – tendons/ligaments
theextracellular matrix(ECM) is athree-dimensionalnetwork consisting ofextracellularmacromoleculesand minerals, such ascollagen,enzymes,glycoproteinsandhydroxyapatitethat provide structural andbiochemicalsupport to surrounding cells.
ECM composition
Matrix macromolecules are secreted by fibroblasts
Composed of 3 major classes of macromolecules:
Glycosaminoglycans (GAGs) – hyaluronan, chondroitin sulphate
Fibrous proteins – type IV collagen, elastin
Non-collagenous glycoproteins – laminin, fibronectin
GAGs
Unbranched polysaccharide chains composed of repeating disaccharide units
Amino sugar (N-acetylglucosamine or N-acetylgalactosamine) which is usually sulphated linked to uronic acid (glucuronic or iduronic)
Highly negatively charged
Four main types – distinguished by their sugars, the linkage between sugars and number and location of sulphate groups
Hyaluronan
Chondroitin sulphate
Proteoglycans
GAGs covalently linked to a core protein
95% GAG, 5% protein in some cases
Very large molecules
Aggrecan found in cartilage has mwt 3 x 103 kDa, over 100 GAG chains
Fibrous proteins - collagen
Found in abundance in connective tissue
Long, rigid, tri-stranded helical molecule
3 collagen a chains are wound round each other
High hydroxyproline content
The most common motifs in the aa sequence of collagen areglycine-proline-X and glycine-X-hydroxyproline
Fibrous proteins - elastin
Found in abundance in connective tissue
Highlyelasticand allows many tissues in the body to resume their shape after stretching or contracting
Rich inglycineandproline which form mobile regions bounded by crosslinks betweenlysine residues
Non-collagenous glycoproteins
Fibronectin
High mwt dimer joined by SS bond
Binds to integrins
Dependant on repeating RGD sequence on fibronectin
Laminin
Major component of thebasement membrane
Heterotrimeric proteins that contain an α-chain, β-chain and γ-chain
Associated withtype IV collagennetworks
Bind to cell membranes through integrinreceptors
Basement membrane
Thin, tough, flexible sheet of matrix molecules
40-120 nm thick
Lies beneath epithelial cells and surrounds individual muscle cells, fat cells and Schwann cells
Typically contains laminin, type IV collagen, nidoge and perlecan
Fibronectin and type XVIII collagen also common
Thebasement membraneis a thin, pliable sheet-like type ofextracellular matrix, that provides cell and tissue support and acts as a platform for complex signalling
Nidogen is a protein
Perlecan is a proteoglycan
Laminin is the primary organiser of the sheet structure
Bind to integrins on cells by their ‘feet’
Once bound to cells, the laminin ‘heads’ form a 2D network with other laminin molecules
Type IV collagen, nidogen and perlecan join to form a cross-linked network of proteins
