cells must cohere if they are to form an organized multicellular structure that can withstand and respond to the various external forces, what are the 2 main ways by which cells are held together?
- Direct interactions by cell-cell junctions
- within the extracellular matrix by cell-matrix junction
What is extracellular matrix (ECM)?
- a network of proteins and polysaccharide chains secreted by cells
- cell-matrix junction link cytoskeleton of cells to ECM, allowing cells to move through matrix and monitor changes in its mechanical properties
- ECM and the cells distributed sparsely within it form the connective tissues
What is the main stress bearing component in connective tissues?
- ECM
- tensile strength comes from collagen
What is the main stress bearing component in epthelial tissue?
The cytoskeleton of the cells that is anchored to cell-cell junction, connecting cells together
How is the epithelial tissue linked to the basal lamina?
cytoskeleton of epithelial cells is linked to basal lamina via cell-matrix junction
What is basal lamina
- thin mat under epethelial tissue
- specialised extracellular matrix of epithelial tissue
- consists mainly of laminins, type IV collagen, entactin, perlecan
- mechanical strength
- perlecan crosslinks the elements of basal lamina
What are the main types of cell junctions?
- tight junctions
cell-cell anchoring junctions:
- adherens junctions
- desmosome
chanel-forming junctions:
- gap junction
cell-matrix anchoring junctions:
- hemidesmome
- actin-linked cell-matrix junction
What is the function of tight junctions?
- holds cell together near appex
- seal gap between cells
- prevent leakage of molecules
Describe tight junctions
- branching network of sealing strands
- each seal strand a long row of transmembrane adhesion proteins (mainly claudins)
What is the function of gap junctions?
- create channels between cells
- allow small water soluble molecules and ions to pass through
describe gap junctions
- consist of channel-forming proteins connexins
- 6 connexins assemble to form 1 connexon
- two connexons of adjacent cells align to form aqueous channel
- gap junction has many pairs of connexons in paralell, forming sieve
- conformational change depend on [Ca2+]: low [Ca2+] open, high [Ca2+] close
What is the function of adherens junction?
- joins actin bundle in one cell to that of the next cell
- tissue remodelling
How does adherin junction link actin filaments of cells together?
cytoplasmic cadherin tail binds to p120-catenin and β-catenin, β-catenin binds to α-catenin, α-catenin recruits actin-binding proteins
Adheren junctions often occur in the form of adhesion belts in epithelial tissues, describe adhesion belts.
- a belt of actin and myosin filament ring on inner surface of cells
- contractionof actin and mysosin bundles allow for constriction in adhesion belts
- important for folding of epithelial tissue into tubes
What is the function of desmosome?
- Joins intermediate filaments in one cell to that of the next cell
- provide mechanical strength
How does desmosomes link intermediate filaments of cells together?
cadherins link to intermediate filaments through adaptor proteins such as plakoglobins and desmoplakin
what is the function of hemidesmosome?
anchors intermediate filaments of cell to the basal lamina
How does hemidesmosomes link intermediate filament of cells to ECM?
- via transmembrane glycoprotein integrin
- integrin binds to adaptor protein plague, which binds to intermediate filaments
what is the function of actin-linked cell-matrix junction?
anchors actin bundle of cell to basal lamina
What are the main transmembrane adhesion proteins?
two main superfamilies: cadherin (cell-cell) and intergrin (cell-matrix)
What are the models of cell-cell adhesion?
- homotopic: interaction within same plasma membrane surface
- homophillic: interaction of the same type of adhesion molecules between different cells
- heterophillic: interaction of different adhesion proteins between different cells
Describe cadherin
- interaction between cadherins is Ca2+ dependent: high [Ca2+] –> rigid, strong interactions
- weak individual interactions, strong collective strength –> avidity
- binds to adaptive proteins by their intracellular domain
Describe integrin
- alpha and beta subunits
- binds to collagen of ECM and cytoskeleton of cells
- mutliple interaction interfaces –> avidity
- cell signalling:
- takes signal outside cell, relay signal inside cell
- takes signal inside cell, relay signal outside cell
- signals by conformational changes: in active state, cytoplasmic tails of alpha and beta subunits are brought apart, allowing the extracellular domain to extend
describe collagen
- secreted by fibroblast
- triple stranded helical structure
- rich in glycine (flexibility) and proline (specificity)
- extremely strong
