Neurofilament transport kinetics can be explained by the activity of small numbers of independent kinesin and dynein motors.

Neurofilaments, which are intermediate filaments, are long flexible protein polymers that are transported bidirectionally along microtubule tracks in axons. Kymograph analysis of neurofilaments has revealed rapid intermittent movement with average run lengths that are consistent with the processive bouts of single motors, and frequent pauses and reversals that suggest rapid switching between opposing motors. To explore this, we used discrete stochastic models of kinesin and dynein motors to model neurofilament movement by teams of independent motors in axons. We describe an unbiased automated sampling algorithm to identify the numbers of kinesin and dynein motors required to match the range of pause times, run times, run lengths, and velocities for neurofilaments in a large dataset of ∼37,000 runs and pauses acquired with 30.3 millisecond resolution. We find that the diverse kinetic behavior of neurofilaments can be explained by the activity of 1-2 kinesin or dynein motors which interact indirectly via the mechanical forces they exert on the neurofilament cargo. Simultaneous engagement of opposing motors was rare in our simulations, indicating that the motile behavior can be explained by alternating kinesin and dynein activity without a competition between motors of opposite directionality.