Cell-substrate interactions

Question 1

extracellular matrix

Answer 1

collection extracellular molecules providing structural and biochemical support to surrounding cells

dynamic and continuously interacting with cells

Question 2

components of the ECM

Answer 2

collagen
elastin
proteoglycans
glycoproteins: fibronectin, laminin

Question 3

integrins

Answer 3

major receptors for cell adhesion
4 categories: collagen receptors, RGD receptors (fibronectin, fibrinogen), laminin receptors, leucocyte specific receptors

interact with actin cytoskeleton

Question 4

matrix metalloproteinases

Answer 4

zinc-dependent endopeptidases
degrade large set substrates

pro-peptide cleavage required for MMP activation

Question 5

tissue inhibitors of metalloproteinases

Answer 5

cysteine complexed with zinc, bind to MMP on active site to inhibit activity

TIMP2 links MMP2 and MMP14, allowing MMP2 activation. too much TIMP2 inhibitory - no free MMP14 to cleave pro-peptide from MMP2

Question 6

ECM and tumour formation

Answer 6

ECM degredation is a crucial step in metastasis formation

primary tumour degrades basal lamina so cells can escape. cells stem in ECM and degrade basal lamina around vessels to enter vessels to travel distant site. Then degrade ECM there to grow

Question 7

ECM degradation assays

Answer 7

zymography

fluorescent based

fluorescent/quenched based

Question 8

ECM cell invasion assays

Answer 8

transwell
3D migration

Question 9

concept tissue engineering

Answer 9

take cells from patient, or a donor and expand them in culture within a scaffold. Will provide a similar structure to the tissue being regenerated.

cells are seed in scaffold and cultured in bioreactor

can then be implanted into body at site of defect