Cell Adhesion 2 - Adhesion to the ECM Flashcards
is adhesion to the ECM permanent?
- no
- as cells need to migrate
What are integrins?
- connect the cell to the ECM
- heterodimers
- transmembrane proteins
- one end connects to fibronectin which connects to ECM
- other end attaches to adaptor proteins which attach to actin (cytoskeleton)
Why is integrin connected to the cytoskeleton?
without this connection it would be flimsy
What is fibronectin?
- dimer connected by disulphide bridge
- cell attachment site - where integrins attach
- ECM binding site - where collagen binds
What is the structure of integrin?
- heterodimer
- alpha sub-unit
- beta sub-unit
What is the innactive conformation of integrin?
folded
What is the active conformation of integrin?
- stretched
- when bound to fibronectin
Explain integrin regulation
inactive - folded
active - stretched
- reversible change - allows cells to move across ECM
How many different kinds of integrin do humans have?
24
how do integrins coordinate cell movement?
- new attachments made at front of cell
- old adhesions released at the back
- actin forms bonds with ECM in direction of movement and releasing them at the back
What is the role of collagen in the ECM?
tensile strength - resist stretching
What is the role of glycosaminoglycans (GAGs)
- resist compression - opposite of collagen
What is the structure of proteoglycans?
glycosaminoglycans (GAGs) join to core protein
How do glycosaminoglycans resist compression?
- GAGs are negative
- attract cations in the ECM
- draw in water
- swelling pressure
- resisting compression
how do collagen and GAGs work together in the ECM?
- tension in collagen
- balanced by GAG swelling
- resulting matrix is tough and resistant to pressure
Name a body part glycosaminoglycans are common?
cartilage
Are GAGs hydrophilic or hydrophobic?
hydrophilic
- space fillers in connective tissue
What are others functions of proteoglycans?
- binding growth factors
- controlling migration of cells through ECM
Explain tissue specific ECM composition
dense connecting tissues (tendon and bone) -> les GAG, more collagen. CaPO4 crystals in bone
vitreous humour -> made almost entirely of GAG, very little collagen
What is an epithelium?
a sheet of cells joined together side by side. It covers all external surfaces and lines all internal cavities
What are 4 different forms of epithelia and their functions and where you would find them?
columnar - secretion / absorption - intestinal lining
cuboidal - secretion / absorption - lining of kidney tubules
squamous - filtration - lining of lung
stratified - protection - epidermis of the skin
What is the basal lamina?
- thin tough sheet of ECM
- separates epitaxial cells from collagen fibres in connective tissue
where’d epithelial cells sit?
on the basal lamina
What is the structure of the basal lamina?
- type IV collagen and laminin
- collagen supplied by underlying stromal cells (connective tissue)
- laminin is supplied by overlying epithelial tissue
What are stromal cells?
mesenchymal cells that make connective tissue
What are mesenchymal cells?
Cells that differentiate into connective tissue
What is the structure of laminin?
heterotrimers made of 3 sections
What is the role of laminin?
- interacts with proteins such as integrin
- provides adhesive sites for integrins located in the basal membrane of epithelial cells
- does a similar job to fibronectin in the connective tissue
Explain epithelial polarity
two faces:
- apical - exposed to the lumen, air and bodily fluids
- basal - connected to the basal lamina
Explain epithelial polarity in the gut
- absorptive epithelial cells
- secretory goblet (mucous) epithelial cells
- different functions in same epithelial sheet
- cells are polarised
What are tight junctions?
- segregate membrane proteins
- prevents membrane proteins moving around the cell, maintaining its polarity
What is the role of tight junctions in epithelial sheets?
- allows them to function as barriers
- binds epithelial cells to prevent leakage
How has the role of tight junctions in epithelial cells been proven?
- extracellular tracers stopped by tight junctions
What forms tight junctions?
- occluding
- claudin
Explain the role of tight junctions in the gut
- Na+ active transport of glucose from the gut lumen
- passive transport into the bloodstream
- tight junctions prevents two transporters moving around the cell, maintaining polarity