1. Cell Communities1 Chapter 20 Key topics Structure & function of -- the extracellular matrix -- cell junctions Tissue organization Properties of -- Stem cells -- Cancer cells Questions in this chapter you should be able to answer: Chapter 20: all

2. Cell Communities2 Extracellular Matrix – I Plant cell wall Composition cellulose hemicellulose lignin Organization Middle lamella 1 O wall 2 O wall Plasmadesmata

3. Cell Communities3 How are cellulose fibers synthesized and oriented? Cellulose organization Cellulose synthase -- pushed forward Microtubule tracts – constrain movement Cellulose fibers Microtubules

4. Cell Communities4 Animal tissue organization Epithelia Extracellular matrix -- Basal lamina -- Connective tissue Epithelia have polarity Tight junctions separate apical vs basal surfaces apical

5. Cell Communities5 What are the 1 O components of the ECM? Collagens Proteoglycans Collagens structure (Glc - X - Y) X often proline Y often hydroxyproline function organization many types Gelatin Scurvy Vitamine-C prolyl-hydroxylase  hydroxyproline Fibroblasts Collagen

6. Cell Communities6 What are proteoglycans? Polysaccharide core (hyaluronate) + Protein linkers + GAG branches (glucoseaminoglycan) GAGs -- Repeating disaccharides -- cationic -- e.g., Chondroitin Functions hydroscopic swelling pressure influence cell migration

7. Cell Communities7 How are cells linked together and to extracellular matrix? May involve Cytoskeleton and components Of extracellular matrix

8. Cell Communities8 What creates Cell-Cell linkages? Cadherins mediate cell-cell linkage -- many types: C-, E-, P-, T- cadherins -- “homophillic” binding Can be connected to cytoskeleton Desmosomes – intermediate filaments Adherin junctions – actin filaments Classic newt embryo experiment -- Townes and Holfreter (1955) (simplified) Cadherins

9. Cell Communities9 Linkage to the ECM are also important Integrins – mediate linkages between cytoskeleton and ECM Also can be connected to cytoskeleton Hemidesmosomes – intermediate filaments Contact Adhesions – actin filaments linkages are ‘responsive’ Question 20-4 Why are these linkages more common in fibroblasts, and desmosomes and adherin junctions more common in epithelial cells?

10. Cell Communities10 How does tissue renewal occur? Cell division vs stem cells e.g., Liver vs skin What are the properties of stem cells? Self renewal Developmental commitment Precursor  terminally differentiated

11. Cell Communities11 Somatic vs Embryonic Stem (ES) cells Somatic – tissue specific -- degrees of commitment -- multipotent vs unipotent ES – any developmental fate -- must follow developmental pathway -- else neoplasm

12. Cell Communities12 How do somatic stem cells renew skin? Skin structure -- stratified epithelium Epidermal stem cells Example of a stratified epithelium

13. Cell Communities13 How do somatic stem cells renew intestine? intestine structure Epithelial stem cells How is pattern of tissue regeneration different than for skin? -- Is intestinal epithelium simple or stratified?

14. Cell Communities14 Stem cell biotechnology Tissue repair -- CNS injury -- burns -- disease (macular degeneration) Organ replacement? -- in vitro regeneration ES-cells

15. Cell Communities15 Why do cells become tumorous? Which type of cancer gene causes loss of cell division control? Which type of cancer gene leads to genetic instability? Which type of mutation requires two altered alleles to exert it’s effect? -- How does LOH overcome this constraint Meningioma karyotype LOH - #17 (Loss Of Heterogenecity) Aneuploidy - #s 9, 7, and 20 Translocation/duplication - #s 2 and 6

16. Cell Communities16 How does loss of genetic stability lead cells to become cancerous?? Benign tumor vs Malignant tumor vs Cancer Evolutionary process Lost dependence of extracellular regulation -- checkpoint failure Loss of ‘mortality’ (e.g., telomere renewal) Activation of genes for motility and invasiveness -- cell junction breakage -- cytoskeletal changes Altered metabolism -- higher glycolysis, less Krebs – why? Abnormal adhesion proteins -- cadherins, etc -- growth in new areas