<?xml version="1.0" encoding="UTF-8"?>
<opml version="2.0">
  <head>
    <title>082-02 Cytoskeleton, cell adhesion, extracellular matrix, polarity, and migration</title>
    <ownerName>Integrated Medical Foundations</ownerName>
  </head>
  <body>
    <outline text="Cytoskeleton, adhesion, matrix, and migration">
      <outline text="Three filament systems">
        <outline text="Shape is an active mechanical state"/>
        <outline text="Actin, microtubules, intermediate filaments"/>
        <outline text="Linked by cross-linkers, motors, adhesions"/>
      </outline>
      <outline text="Actin and myosin">
        <outline text="Polar filaments with plus and minus ends"/>
        <outline text="Arp two-three branches, formins make long filaments"/>
        <outline text="Profilin adds monomers, cofilin drives turnover"/>
        <outline text="Cortex resists deformation"/>
        <outline text="Bundles: microvilli, stereocilia, stress fibres">
          <outline text="Stereocilia are actin, true cilia microtubule"/>
        </outline>
        <outline text="Spectrin defects cause haemolysis"/>
        <outline text="Myosin two contracts actin networks">
          <outline text="Filament polarity sets motor direction"/>
        </outline>
      </outline>
      <outline text="Microtubules and cilia">
        <outline text="Hollow alpha-beta tubulin polymers"/>
        <outline text="Dynamic instability searches cytoplasm">
          <outline text="Cap loss triggers catastrophe"/>
          <outline text="Rescue restores growth"/>
        </outline>
        <outline text="Centrosome organises bipolar spindle"/>
        <outline text="Kinesins to plus ends, dynein to minus ends">
          <outline text="Defects cause distal axon degeneration"/>
        </outline>
        <outline text="Motile cilia: nine-plus-two, clear mucus"/>
        <outline text="Primary cilia: nine-plus-zero, sensing">
          <outline text="Defects: infection, infertility, laterality"/>
        </outline>
      </outline>
      <outline text="Intermediate filaments">
        <outline text="Nonpolar ropes with high tensile strength"/>
        <outline text="Keratins in epithelia, vimentin in mesenchyme"/>
        <outline text="Desmin in muscle, neurofilaments in axons"/>
        <outline text="Glial fibrillary acidic protein in astroglia"/>
        <outline text="Tissue-specific expression aids diagnosis"/>
        <outline text="Mutations: blistering, weakness, degeneration"/>
      </outline>
      <outline text="Adhesion and junctions">
        <outline text="Cadherins: calcium-dependent cell-cell adhesion"/>
        <outline text="Integrins bind matrix, regulated both ways"/>
        <outline text="Adherens junctions link cadherins to actin"/>
        <outline text="Desmosomes link to intermediate filaments"/>
        <outline text="Hemidesmosomes anchor to basement membrane">
          <outline text="Separation level defines blistering disease"/>
        </outline>
        <outline text="Tight junctions seal paracellular path">
          <outline text="Claudins set selectivity"/>
          <outline text="Fence between apical and basolateral"/>
        </outline>
        <outline text="Gap junctions: connexin channels">
          <outline text="Electrical coupling synchronises muscle"/>
        </outline>
      </outline>
      <outline text="Extracellular matrix">
        <outline text="Instructive environment, not inert packing"/>
        <outline text="Collagen strength, elastin recoil, proteoglycan water"/>
        <outline text="Collagen hydroxylation needs vitamin C"/>
        <outline text="Basement membrane: type four collagen, laminin">
          <outline text="Invasion requires breaching it"/>
          <outline text="Intact scaffold aids orderly repair"/>
        </outline>
        <outline text="Metalloproteinases balanced by inhibitors">
          <outline text="Excess degradation: aneurysm, arthritis"/>
          <outline text="Persistent injury: scar replaces tissue"/>
        </outline>
      </outline>
      <outline text="Epithelial polarity">
        <outline text="Apical and basolateral domains"/>
        <outline text="Junctions, cytoskeleton, trafficking reinforce"/>
        <outline text="Vectorial transport needs correct placement"/>
        <outline text="Polarity loss is early in dysplasia"/>
      </outline>
      <outline text="Migration and invasion">
        <outline text="Protrusion, adhesion, traction, rear release">
          <outline text="Rho-family small GTPases coordinate regions"/>
        </outline>
        <outline text="Chemotaxis, haptotaxis, durotaxis"/>
        <outline text="Leukocyte capture, rolling, adhesion, transmigration">
          <outline text="Selectins roll, chemokines activate integrins"/>
          <outline text="Adhesion defects block tissue entry"/>
        </outline>
        <outline text="Epithelial-to-mesenchymal programme is a spectrum">
          <outline text="Metastasis also needs survival and a new niche"/>
        </outline>
      </outline>
      <outline text="Mechanotransduction">
        <outline text="Force converted to biochemical response"/>
        <outline text="Sensors: integrins, cadherins, channels, lamina"/>
        <outline text="Bone, muscle, vessels adapt to load"/>
        <outline text="Abnormal force: fibrosis, osteoarthritis"/>
        <outline text="One mutation alters strength and signalling"/>
      </outline>
    </outline>
  </body>
</opml>
