Strain-dependent kinetics of the myosin working stroke, and how they could be probed with optical-trap experiments
David A Smith 1* and John Sleep 2
1 Monash University
2 King's College London
* To whom correspondence should be addressed. E-mail: david.smith{at}med.monash.edu.au.
Submitted on March 20, 2006
Revised on May 2, 2006
Accepted on 16 June 2006
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Abstract |
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The strain-dependent kinetics of the myosin working stroke under load is derived from a flat-energy-landscape model for its untethered lever-arm, and compared with other scenarios in the literature. The 'flat-landscape' scenario is compatible with muscle-fibre experiments, but is more critically relevant to single-myosin experiments with an optically-trapped actin filament. In such experiments, the strain-dependence of stroke kinetics may be explored by comparing event-averaged and time-averaged displacements of the filament. With a specific kinetic model of the crossbridge cycle, we have previously shown that the event-averaged displacement underestimates the working stroke. Here we predict that the two kinds of averaging give diverging estimates of the working stroke as the resolving time of the event detector is decreased to 1ms or less, the discrepancy being critically dependent on the strain-dependence of the stroke rate. Such analysis of trap displacement data offers the possibility of testing the strain-dependent stroke rate predicted by the flat-landscape model.
Key Words:
kinetics, myosin, strain, stroke, traps