Effectiveness of a dynein team in a tug of war helped by reduced load sensitivity of detachment: evidence from the study of bidirectional endosome transport inD. discoideum

Abstract

Bidirectional cargo transport by molecular motors in cells is a complex phenomenon in which the cargo (usually a vesicle) alternately moves in retrograde and anterograde directions. In this case, teams of oppositely pulling motors (e.g., kinesin and dynein) bind to the cargo, simultaneously, and 'coordinate' their activity such that the motion consists of spells of positively and negatively directed segments, separated by pauses of varying duration. A set of recent experiments have analyzed the bidirectional motion of endosomes in the amoeba D. discoideum in detail. It was found that in between directional switches, a team of five to six dyneins stall a cargo against a stronger kinesin in a tug of war, which lasts for almost a second. As the mean detachment time of a kinesin under its stall load was also observed to be ∼1 s, we infer that the collective detachment time of the dynein assembly must also be similar. Here, we analyze this inference from a modeling perspective, using experimentally measured single-molecule parameters as inputs. We find that the commonly assumed exponential load-dependent detachment rate is inconsistent with observations, as it predicts that a five-dynein assembly will detach under its combined stall load in less than a hundredth of a second. A modified model where the load-dependent unbinding rate is assumed to saturate at stall-force level for super-stall loads gives results which are in agreement with experimental data. Our analysis suggests that the load-dependent detachment of a dynein in a team is qualitatively different at sub-stall and super-stall loads, a conclusion which is likely to have implications in other situations involving collective effects of many motors.

Gene Electrotransfer: A Mechanistic Perspective

“…16, step 5). The quantified fast velocities corresponded well to the known mean velocities of dyneins, 220-1200 nm/s, and kinesins, 200 nm/s to 1600 nm/s [298-300]. Colocalization between DNA trajectories and microtubules and between DNA aggregates and the dynein motor supported these findings [230].…”

“…14 ). Single dynein, kinesin and myosin motors are described to run over distances from a few hundreds of nanometers to 2 µm with transport durations of less than 3 s [293-295, 298, 300, 303]. The longer travelled distances and the larger persistence of travelling measured suggest that DNA aggregates are driven by multiple motors of the same type, as is normally the case for cellular cargo transport [304, 305].…”

Intracellular Tracking of Single-plasmid DNA Particles After Delivery by Electroporation

“…By contrast, much higher velocities with mean values of 220-1,200 nm/second have been observed for dyneins and for kinesins velocities ranging from 200 to 1,600 nm/second have been reported. [35][36][37] We therefore assume that the fast active transport we observe is driven by microtubulerelated motors of the dynein and kinesin families (Figure 5, step 6a). This interpretation is further supported by the observed colocalization between DNA trajectories and the microtubules and the colocalization between DNA and the dynein motor (Supplementary Figure S4).…”

Memory, bias, and correlations in bidirectional transport of molecular-motor-driven cargoes

“…For details of the simulations including the fixing of binding and unbinding rates and determination of the velocity of cargo motion, the reader is referred to our earlier paper [20].…”

“…1(a) (see ref. [20] for details). Such a motion may be visualized as a biased random walk [21], with unidirectional runs separated by pause states.…”