mechanotransduction and tensegrity
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Mechanotransduction and Tensegrity. ChemEng 590B: Lecture 12 March 28 th , 2013. Mechanotransduction: Cell can translate Mechanical Information from the ECM to an intracellular biochemical signal. “ Mechanotransduction ”. OUTSIDE- IN (ECM-initiated). INSIDE- OUT (cell-initiated). - PowerPoint PPT PresentationTRANSCRIPT
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Mechanotransduction and Tensegrity
ChemEng 590B: Lecture 12March 28th, 2013
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Mechanotransduction: Cell can translate Mechanical Information from the ECM to an intracellular biochemical signal
“Mechanotransduction”
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OUTSIDE-IN (ECM-initiated) INSIDE-OUT (cell-initiated)
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Example: outside in signalingUsing a probe to vibrate substrate under cell
Nishitani, PLOS 1
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Outside-In. Cytoskeleton in response to stretch
Putnam et al., JCS, 1998
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Outside-In. Forces directly on the cell or through the ECM are transduced through the cytoskeleton
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Inside-Out Signaling• Cell is constantly probing microenvironment by assembling and
disassembling adhesions
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Matrix Stiffness and Focal AdhesionsStretchable silicon dish (Flexcell)
Cas activated with stretch – is Src dependent
• Cas activates Rap1 (GEF), previous work• Hypothesis: Cas is phosphorylated by SFK,
only during stretch• COOH domain of Cas anchored to a FA (Talin
and FAK)• NH2 end is connected to actin filament, and is
stretched during actin force generation
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Matrix Stiffness and Focal Adhesions
• Cas activates Rap1 (GEF), previous work• Hypothesis: Cas is phosphorylated by
SFK, only during stretch• One end connected to more static FA• SH3 domain of Cas anchored to a FA
(Talin and FAK) and actin actin filament, and is stretched during actin force generation
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…Or, Behavior Could be Dictated by a Cell-ECM Force Balance…
• In response to extracellular stretch or an intrinsic ECM stiffness, F-actin microfilaments adjust in tensional resistance, and the microtubule network adjusts in compressive resistance.
Courtesy of A. Putnam
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Tensegrity: a Physical Mechanism of Mechanotransduction
Hypothesis 1: tensegrity (Don Ingber) and pre-stress (Ning Wang)
Cytoskeleton connects from focal adhesions to nucleus.Forces at focal adhesions can propogate to changes in shape of nucleus affects transcription regulators gene expression/phenotype
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Microtubules Resist Compressive Forces
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Traction Force Microscopy: Tool to Measure Cellular Forces Exerted on Substrate
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Matrix Stiffness and Focal AdhesionsTraction Force Microscopy
With external pull, stable FAs don’t’ increase in size
Traction stress increases even after FAs stop growing
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