Crowding and pausing strongly affect dynamics of kinesin-1 motors along microtubules

TL;DR

This study uses an agent-based lattice gas model to investigate how crowding and pausing influence kinesin-1 motor dynamics on microtubules, revealing the impact of traffic jams and inactive states on motor behavior.

Contribution

It introduces a quantitative model that links motor interactions, crowding effects, and pausing behavior, providing new insights into kinesin-1 collective dynamics.

Findings

Model accurately predicts concentration-dependent motor characteristics.

Kinesin-1 motors often enter an inactive, weakly bound state.

Traffic jams amplify the effects of inactive motors on movement.

Abstract

Molecular motors of the kinesin-1 family move in a directed and processive fashion along microtubules (MTs). 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 which 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 which 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 MT.