Tuning Multiple Motor Travel via Single Motor Velocity

Abstract

Microtubule-based molecular motors often work in small groups to transport cargos in cells. A key question in understanding transport (and its regulation in vivo) is to identify the sensitivity of multiple-motor-based motion to various single molecule properties. Whereas both single-motor travel distance and microtubule binding rate have been demonstrated to contribute to cargo travel, the role of single-motor velocity is yet to be explored. Here, we recast a previous theoretical study, and make explicit a potential contribution of velocity to cargo travel. We test this possibility experimentally, and demonstrate a strong negative correlation between single-motor velocity and cargo travel for transport driven by two motors. Our study thus discovers a previously unappreciated role of single-motor velocity in regulating multiple-motor transport.

Elastic Coupling Effects in Cooperative Transport by a Pair of Molecular Motors

“…As a consequence, the cargo run length now exhibits the opposite behavior as in the case above. Figure 6f shows that the run length is strongly increased for decreasing single motor velocities, as the probability of having both motors bound to the filament increases strongly due to the reduction of the unbinding rate 2 : This is exactly the effect observed by Xu et al 63 with two kinesin motors, who found the run length of two coupled motors to increase when the single motor velocity was decreased.…”

“…independent of the ATP concentration over a rather wide range of ATP concentrations, 59,63 contrary to what one would expect if the ATP concentration only affected the velocity. This observation indicates that a variation of the velocity via the ATP concentration also leads to a variation of the single motor unbinding rate 1 : It can be explained using models for the chemomechanical cycles of kinesin, 46 which also show that this type of dependence is only expected for low concentrations of ADP and inorganic phosphate.…”

“…This feature has some interesting consequences for coupled motors that have been addressed experimentally in a recent study for two kinesins coupled via an antibody. 63 We note however that the run length becomes dependent on the ATP concentration if the ATP concentration is sufficiently low; 56 here, what concentration is sufficiently low depends on the concentration of inorganic phosphate in the buffer. 46 To discuss this issue within our theoretical framework, we consider a second mode of varying the single motor velocity.…”

“…For the first two systems a binding rate of '5/s 3,44 was found, while the latter resulted in smaller binding rates. 53,63 The parameters 2 and v 2 that characterize state C 2 are even less straightforward. In the case of non-interacting motors, in which the motors step independently of each other, we obtain v 2 = v 1 and 2 ¼ 2 1 ; since the rate for an unbinding event when both motors are bound, is the sum of the single rates.…”

“…An important improvement for studying motor cooperation was thus the design of synthetic assemblies of precisely defined numbers of motors. 48,53,63 Since then a number of studies have investigated such defined motor complexes: The most extensive studies have been done for a system of two kinesin-1 motors coupled via a DNA scaffold, 34,53 but other studies have also used two kinesins coupled via an antibody, 63 two coupled myosin V motors, 48 and a myosin V motor coupled to a myosin VI motor. 1 Motor cooperation has also been studied with microtubule gliding assays, in which motors immobilized on a surface pull a microtubule along that surface.…”