Crowding and Pausing Strongly Affect Dynamics of Kinesin-1 Motors along Microtubules.

Molecular motors of the kinesin-1 family move in a directed and processive fashion along microtubules. It is generally accepted that steric hindrance of motors leads to crowding effects; however, little is known about the specific interactions involved. We employ an agent-based lattice gas model to study the impact of interactions that enhance the detachment of motors from crowded filaments on their collective dynamics. The predictions of our model quantitatively agree with the experimentally observed concentration dependence of key motor characteristics including their run length, dwell time, velocity, and landing rate. From the anomalous stepping statistics of individual motors that exhibit relatively long pauses, we infer that kinesin-1 motors sometimes lapse into an inactive state. Hereby, the formation of traffic jams amplifies the impact of single inactive motors and leads to a crowding dependence of the frequencies and durations of the resulting periods of no or slow motion. We interpret these findings and conclude that kinesin-1 spends a significant fraction of its stepping cycle in a weakly bound state in which only one of its heads is bound to the microtubule.