molecular motors jean v bellissard georgia institute of technology school of physics fall 2015
TRANSCRIPT
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Molecular Motors
Jean V BellissardGeorgia Institute of Technology
School of PhysicsFall 2015
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Cell Activity
• Cell division: chromosome replicate, segregate into two daughter cells
• Flagella: wiggle around to move sperm, cilia beats to avoid accumulation of mucus in lungs
• Nerve cells: fire by vesicle moving around to deliver neurotransmitters
• How do such movements happen ?
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Molecular Motors
• Fuel: Adenosine Triphosphate (ATP) is the cellular source food• Engine: proteins using the ATP to move
• How far do they move? 1. few microns in typical cells2. about a meter along nerves
• Efficiency: how come they operate at about 100% efficiency ? (!!!)
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Myosin-Actin in muscle cells
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Kinesin-Microtubule in cells
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Kinesin-Microtubule in cells
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Dynein-Microtubule in cells
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Kinesin-microtubule experiments
• P.R. Selvin’s group (U. Illinois, Urbana-Champaign) led a series of experiments between 2002-07 to measure the movement of the kinesin.
• The protein is walking like a human being.
• Steps are 8.3 nm long
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• A light microscope cannot discriminate a distance less than 250nm!
• A new technique called Fluorescence Imaging with One Nanometer Accuracy was developed (FIONA, Ahmet Yildiz).
• FIONA has a spatial resolution of 1.5nm!!
• Myosin, kinesin and dynein move in hand-over-hand fashion, namely they walk!
Kinesin-microtubule experiments
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Kinesin-microtubule modeling
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Adenosine-triphosphate (ATP)
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Adenosine-triphosphate (ATP)
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Adenosine-triphosphate (ATP)
• ATP ® ADP, AMP hydrolysis (Pi=phosphate, Ppi=pyrophosphate)
• ATP + H2O → ADP + Pi ΔG˚ = −30.5 kJ/mol
(−7.3 kcal/mol) • ATP + H2O → AMP + PPi ΔG˚ =
−45.6 kJ/mol (−10.9 kcal/mol)
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Adenosine-triphosphate (ATP)
• Living cells maintain the ratio of ATP to ADP at a point ten orders of magnitude from equilibrium, with ATP concentrations fivefold higher than the concentration of ADP.
• The hydrolysis of ATP in cells release a large amount of free energy
• Dm=mATP-mADP-mP is large @ 10kBT
(non-linear regime) [exp(-Dm/kBT)=e-10 ]
• fext=external force (friction, cargo)
• r = ATP consumption rate, • v = velocity of the protein
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• Microtubules are rigid, periodic with
period @ 10nm, polar, asymmetric. • Fastest motor characteristic time
O(1ms). Return to equilibrium time O(100ns).
• Local equilibrium approximation applies.
• Each protein molecule can be in at least 2 states depending upon the presence of ATP.
Protein-microtubule modeling
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Protein-microtubule modeling
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Protein-microtubule modeling
Ratchet model
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Protein-microtubule modeling
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Protein-microtubule modeling
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Protein-microtubule modeling
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