BIOMED SCIE LECTURE 29 MACHANOBIOLOGY AND CANCER

• Mechanobiology


  The study of the essential roles that physical factors play via the process of mechanotransduction
• Mechanotransduction


  The process by which cells convert mechanical stimuli into biochemical signalling events

  
• Mechanosensing


  The mechanical alteration of protein conformation to control cell function
• Mechanosensing


  • No force
  • Cytoplasmic
  • Extracellular
  • Plasma membrane
  • Syndecan-4 homodimer
• Biophysical cues


  Alter stem cell differentiation
• Stiffness


  Alters stem cell differentiation
• Sensing force


  Leads to changes in cell shape

  
• Integrin-based adhesion complexes


  • Recognise not only the biochemical factors of the extracellular surroundings, but also their physical and geometrical characteristics such as elasticity, dimensionality and ligand spacing

  
• Cytoskeleton


  • Network of three types of protein filaments: microfilaments, intermediate filaments, microtubules
• Focal adhesion mechanotransduction


  Cytoskeletal tension and matrix stiffness support focal adhesion growth (maturation)
• Viscoelastic


  Biological tissues and extracellular matrices exhibit this property

  
• Stress relaxation


  Biological tissues and extracellular matrices exhibit this in response to deformation

  
• ECM stiffness


  Influences cell traction forces, which can induce epithelial-mesenchymal transition (EMT) to influence processes like wound healing, angiogenesis and metastasis

  
• Pancreatic cancer


  • Associated with an explosion in collagen and other matrix proteins
  • Most of the tumour is connective tissue called stroma
• Stiffness


  Leads to traction force, which leads to EMT, which leads to metastasis
• Organ-on-Chip models


  • Used to implement mechanobiology