Intracellular Transport of Single-Headed Molecular Motors KIF1A

Motivated by experiments on single-headed kinesin KIF1A, we develop a model of intracellular transport by interacting molecular motors. It captures explicitly not only the effects of adenosine triphosphate hydrolysis, but also the ratchet mechanism which drives individual motors. Our model accounts for the experimentally observed single-molecule properties in the low-density limit and also predicts a phase diagram that shows the influence of hydrolysis and Langmuir kinetics on the collective spatiotemporal organization of the motors. Finally, we provide experimental evidence for the existence of domain walls in our in vitro experiment with fluorescently labeled KIF1A.

Figure 1

The biochemical and mechanical states of a single KIF1A motor. On the left of the dotted line, KIF1A is bound to a fixed position on the MT (state 1), while on the right it diffuses along the MT track (state 2). At the transition from state 1 to 2, KIF1A detaches from the MT.

Figure 2

A 3-state model for molecular motors moving along a MT. 0 denotes an empty site, 1 is K or KT, and 2 is KD. Transition from 1 to 2, corresponding to hydrolysis, occurs within a site whereas movement to the forward or backward site occurs only when motor is in state 2. At the minus and plus ends the probabilities are different from those in the bulk.

Figure 3

The stationary density profiles for ${\omega }_h=0.1$ (left) and ${\omega }_h=0.2$ (right) in the case ${\omega }_a=0.001$. The blue and red lines correspond to the densities of state 1 and 2, respectively. The dashed lines are the mean-field predictions (9, 10) for periodic systems with the same parameters.

Figure 4

Phase diagram of the model in the ${\omega }_h\mathrm{\text{−}}{\omega }_a$ plane, with the corresponding values for ATP and KIF1A concentrations given in brackets. These quantities are controllable in experiment. The boundary rates are $\alpha ={\omega }_a$, ${\beta }_{1,2}={\omega }_d$, ${\gamma }_{1,2}=\delta =0$. The position of the immobile shock depends on both ATP and KIF1A concentrations.

Figure 5

Formation of cometlike accumulation of kinesin at the end of MT. Fluorescently labeled KIF1A (red) was introduced to MT (green) at 10 pM (top), 100 pM (middle), and 1000 pM (bottom) concentrations along with 2 mM ATP. The length of the white bar is $2\mu \mathrm{m}$.