Enhancement of cargo processivity by cooperating molecular motors

TL;DR

This paper models how passive motors enhance cargo processivity by either reducing detachment or increasing reattachment rates, with distinct mechanisms for microtubular and actin-based transport, supported by experimental data fitting.

Contribution

It introduces a stochastic model of two-motor cooperation, revealing two distinct mechanisms for processivity enhancement and fitting experimental data to estimate kinetic parameters.

Findings

Passive tether can decrease detachment rate or increase reattachment rate.

Microtubular transport benefits mainly from increased reattachment rate.

Actin transport benefits mainly from reduced detachment rate.

Abstract

Cellular cargo can be bound to cytoskeletal filaments by one or multiple active or passive molecular motors. Recent experiments have shown that the presence of auxiliary, nondriving motors, results in an enhanced processivity of the cargo, compared to the case of a single active motor alone. We model the observed cooperative transport process using a stochastic model that describes the dynamics of two molecular motors, an active one that moves cargo unidirectionally along a filament track and a passive one that acts as a tether. Analytical expressions obtained from our analysis are fit to experimental data to estimate the microscopic kinetic parameters of our model. Our analysis reveals two qualitatively distinct processivity-enhancing mechanisms: the passive tether can decrease the typical detachment rate of the active motor from the filament track or it can increase the corresponding reattachment rate. Our estimates unambiguously show that in the case of microtubular transport, a higher average run length arises mainly from the ability of the passive motor to keep the cargo close to the filament, enhancing the reattachment rate of an active kinesin motor that has recently detached. Instead, for myosin-driven transport along actin, the passive motor tightly tethers the cargo to the filament, suppressing the detachment rate of the active myosin.