BE 167L Lecture 7 General

BE 167L Lecture 7 General - BE 167L – Bioengineering...

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Unformatted text preview: BE 167L – Bioengineering Lab Lecture 7 Today •  Cell Mechanobiology – Basic mechanics – Mechanical measurement techniques – Physiological relevance and response to force – “Mechanical” machinery of cells Tuesday & Thursday Case Study 3: mechanics and differenIaIon Case Study 4: cell ­contact/mechanics and differenIaIon Mechanics – briefly… Stress Normal Stress Strain Young’s Modulus (or Stiffness) σ Tools for Mechanical Measurements Key Concept: Apply Forces to Cells & Measure Response Kim et al. Ann Rev Biomed Eng 2009 Cell Mechanics and the Microenvironment Mechanical Environments •  ConnecIve Issue  ­ fibroblasts •  CarIlage  ­ chrondrocytes •  Bone  ­ osteoblasts •  Blood vessels  ­ endothelial cells, smooth muscle cells •  What mechanical forces do they feel? Mechanical Elements in the Cell •  Cytoskeleton •  Motor proteins  ­ myosins, kinesins, dynein •  Larger scale mechanical structures: – Filopodia, lamellipodia – Focal adhesions – connecIon to ECM •  MechanotransducIon – transducing force into biochemical signals Cytoskeletal Components Functions of the cytoskeleton: (a)  patially organizes the S contents of the cell (b)  onnects the cell physically C and biochemically to the external environment (c)  enerates coordinated forces G that allow the cell to move and change shape microtubules intermediate filaments actin Fletcher et al. Nature 2010 Microtubules •  Persistance length of ~ 5 mm (measure of bending rigidity) •  Tubulin monomers •  Hypothesized to be a compressive load bearing element •  Transports cargo, like DNA (mitosis) •  SIffest filaments Kinesins & Dynein Molecular Motor - Force generator that binds to microtubules Dynein, moves + to - F ­AcIn Barbed end •  Persistance length of ~ 20 µm (much less sIff) •  AcIn monomers •  Hypothesized to be a tensile strut (stress fibers) or force generator on the membrane •  > 100 binding proteins to modify its funcIon Pointed end Myosins Molecular Motor - Force generator that binds to F-actin AcIn and Microtubules are polarized •  Allows unidirecIonal growth •  Generates force •  Allows motors to travel in specific direcIons •  Train tracks for intracellular trafficking •  Allows migraIon and contracIon of cells Intermediate Filaments •  Persistance length of ~ 1 µm (least rigid) Examples •  Various monomers •  Neurofilaments •  Connects to other cytoskeletal elements •  VimenIn •  Not sIff but more resistant to tensile forces •  Lamin •  Least is known about them •  Desmin •  KeraIn Lamellipodia and Filopodia are created by acIn filaments in response to sImuli Various Cell Responses to Force •  Mechanotaxis ­cell migraIon due to gradients of force •  DifferenIaIon ­acquiring developed phenotype/funcIon due to forces (endothelial cells) •  Alignment ­community cytoskeletal organizaIon •  Cell Division Axis ­proliferaIon and development of larger structures Mechanotaxis Directional Migration in Flow Li et al. PNAS 2002 Alignment of cytoskeleton based on shear Endothelial cell Alignment in Flow Ohashi et al. Fluid Dynamics Research 2005 Cell Division Axis depends on cytoskeletal aiachments to ECM Thery et al. Nat. Cell Bio. 2005 ...
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