When observing the spontaneous bead fluctuations, we find that the trajectory consists of phases in which the bead moves persistently in one direction. During such a persistent phase, the kurtosis is positive.
Our physical interpretation is as follows: Since the bead is bound predominantly elastic, the persistent motion means that the force causing this motion is increasing more and more: a force ramp. However, the positive kurtosis indicates that the force increases not continuously, but in steps.
Note that what we need are not force pulses (going up and down), but steps (going up and remaining at the high level, until the next step increases the force even higher). Symetrically, a step-wise decrease of the force would move the bead in the opposite direction.
Biologically, the force steps should have something to do with the assembly/disassembly of acto-myosin stress fibers. My interpretation is as follows:
Upward/downward force steps occur each time when a new (force-generating) building block has been added/removed to one of the acto-myosin fibers.
This building block could be a bunch of myosin motors which have been added/removed to/from the pool of other motors that already contributed to the average fiber force before. It could also be a whole pre-assembled small acto-myosin filament that attaches itself in parallel to an excisting filament bundle.
It is important that the motors are working, at least collectively, in a "processive mode": There should at any moment be a finite average force level and never should all motors simultaneously let go the actin filament.
If we take the "fit parameters" from [AD 12] seriously, in order to achieve in one step a bead displacement of 10 nm, assuming a elastic binding stiffness of 1 nN/um, we need a force step of 10 pN. This is more than what a single myosin motor can probably achieve.
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