--- module: 082-02 language: en chapter: 82 title: "Cell Architecture, Organelles, Cytoskeleton, Trafficking, and the Cell Cycle" module_title: "Cytoskeleton, cell adhesion, extracellular matrix, polarity, and migration" source_sha256: ee0bfae798070682a1fa23be4564f64622e8d8fe58bd3990231a48dedc9c3f32 --- # Cytoskeleton, adhesion, matrix, and migration ## Three filament systems ### Shape is an active mechanical state ### Actin, microtubules, intermediate filaments ### Linked by cross-linkers, motors, adhesions ## Actin and myosin ### Polar filaments with plus and minus ends ### Arp two-three branches, formins make long filaments ### Profilin adds monomers, cofilin drives turnover ### Cortex resists deformation ### Bundles: microvilli, stereocilia, stress fibres #### Stereocilia are actin, true cilia microtubule ### Spectrin defects cause haemolysis ### Myosin two contracts actin networks #### Filament polarity sets motor direction ## Microtubules and cilia ### Hollow alpha-beta tubulin polymers ### Dynamic instability searches cytoplasm #### Cap loss triggers catastrophe #### Rescue restores growth ### Centrosome organises bipolar spindle ### Kinesins to plus ends, dynein to minus ends #### Defects cause distal axon degeneration ### Motile cilia: nine-plus-two, clear mucus ### Primary cilia: nine-plus-zero, sensing #### Defects: infection, infertility, laterality ## Intermediate filaments ### Nonpolar ropes with high tensile strength ### Keratins in epithelia, vimentin in mesenchyme ### Desmin in muscle, neurofilaments in axons ### Glial fibrillary acidic protein in astroglia ### Tissue-specific expression aids diagnosis ### Mutations: blistering, weakness, degeneration ## Adhesion and junctions ### Cadherins: calcium-dependent cell-cell adhesion ### Integrins bind matrix, regulated both ways ### Adherens junctions link cadherins to actin ### Desmosomes link to intermediate filaments ### Hemidesmosomes anchor to basement membrane #### Separation level defines blistering disease ### Tight junctions seal paracellular path #### Claudins set selectivity #### Fence between apical and basolateral ### Gap junctions: connexin channels #### Electrical coupling synchronises muscle ## Extracellular matrix ### Instructive environment, not inert packing ### Collagen strength, elastin recoil, proteoglycan water ### Collagen hydroxylation needs vitamin C ### Basement membrane: type four collagen, laminin #### Invasion requires breaching it #### Intact scaffold aids orderly repair ### Metalloproteinases balanced by inhibitors #### Excess degradation: aneurysm, arthritis #### Persistent injury: scar replaces tissue ## Epithelial polarity ### Apical and basolateral domains ### Junctions, cytoskeleton, trafficking reinforce ### Vectorial transport needs correct placement ### Polarity loss is early in dysplasia ## Migration and invasion ### Protrusion, adhesion, traction, rear release #### Rho-family small GTPases coordinate regions ### Chemotaxis, haptotaxis, durotaxis ### Leukocyte capture, rolling, adhesion, transmigration #### Selectins roll, chemokines activate integrins #### Adhesion defects block tissue entry ### Epithelial-to-mesenchymal programme is a spectrum #### Metastasis also needs survival and a new niche ## Mechanotransduction ### Force converted to biochemical response ### Sensors: integrins, cadherins, channels, lamina ### Bone, muscle, vessels adapt to load ### Abnormal force: fibrosis, osteoarthritis ### One mutation alters strength and signalling