Effect of fuel concentration and force on collective transport by a team of dynein motors

Abstract

Motor proteins are essential components of intracellular transport inside eukaryotic cells. These protein molecules use chemical energy obtained from hydrolysis of ATP to produce mechanical forces required for transporting cargos inside cells, from one location to another, in a directed manner. Of these motors, cytoplasmic dynein is structurally more complex than other motor proteins involved in intracellular transport, as it shows force and fuel (ATP) concentration dependent step-size. Cytoplasmic dynein motors are known to work in a team during cargo transport and force generation. Here, we use a complete Monte-Carlo model of single dynein constrained by in vitro experiments, which includes the effect of both force and ATP on stepping as well as detachment of motors under force. We then use our complete Monte-Carlo model of single dynein motor to understand collective cargo transport by a team of dynein motors, such as dependence of cargo travel distance and velocity on applied force and fuel concentration. In our model, cargos pulled by a team of dynein motors do not detach rapidly under higher forces, confirming the experimental observation of longer persistence time of dynein team on microtubule under higher forces.

Estimating three-dimensional outflow and pressure gradients within the human eye

“…So dynein motors move along microtubules at maximum speed when unrestrained, and they generate maximum pulling force as they stall (they ‘stall’ at some load, meaning their velocity drops to zero) [82, 83]. There is an approximately linear relationship relating dynein’s velocity and dynein’s generated pulling force, the proportionality constant depending on, among other things, the ATP concentration and the number of dynein motors working together in ‘teams’ to generate the pulling force on the load [83, 84].…”

Dynamic catch-bonding generates the large stall forces of cytoplasmic dynein

“…Another modeling study, Takshak et al [37], expanded on the model of Singh et al [6] by incorporating the same static catch-bond detachment kinetics, mostly focused on velocity, run length, and run time of a cargo driven by multiple dynein motors. The predicted average run length decreased with increasing load at high ATP concentrations, which is different from our predictions where the run length can increase with increasing load force at high ATP concentrations.…”

“…Run times, defined as the time before the cargo detached from its track, were almost constant for large load forces due to the static catch-bond of the dynein motors, which is consistent with our model. Most importantly, as in [36] the model of Takshak et al [37] was tuned to stall forces of about 1 pN for a single motor and did not address the observation of larger single-motor stall forces.…”