Coupling between motor proteins determines dynamic behaviors of motor protein assemblies

Abstract

Transport of intracellular cargos by multiple microtubule motor proteins is believed to be a common and significant phenomenon in vivo, yet signatures of the microscopic dynamics of multiple motor systems are only now beginning to be resolved. Understanding these mechanisms largely depends on determining how grouping motors affect their association with microtubules and stepping rates, and hence, cargo run lengths and velocities. We examined this problem using a discrete state transition rate model of collective transport. This model accounts for the structural and mechanical properties in binding/unbinding and stepping transitions between distinct microtubule-bound configurations of a multiple motor system. In agreement with previous experiments that examine the dynamics of two coupled kinesin-1 motors, the energetic costs associated with deformations of mechanical linkages within a multiple motor assembly are found to reduce the system's overall microtubule affinity, producing attenuated mean cargo run lengths compared to cases where motors are assumed to function independently. With our present treatment, this attenuation largely stems from reductions in the microtubule binding rate and occurs even when mechanical coupling between motors is weak. Thus, our model suggests that, at least for a variety of kinesin-dependent transport processes, the net 'gains' obtained by grouping motors together may be smaller than previously expected.

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

“…To tackle this task several groups (including ours) have developed a variety of detailed models for coupled motors. These approaches typically take one of two roads: They either start by splitting the state with two bound motors, C 2 into several substates, 7,14,19,20,37,57,61 in which case some results can still be obtained analytically, or use detailed computational models that particularly emphasize on the geometry of the motor-complex or the arrangement of motors on a bead. 13,39,41 In reference, 37 a detailed chemomechanical network for two-motor complexes is used to generate trajectories and to show that the parameters 2 and v 2 can be deduced in a unique manner from the statistical properties of the trajectories.…”

“…These three processes are characterized by the corresponding rates, which, in principle, could all be force-dependent. However, as in several previous studies 38,50 (but different from others 19,20 ), we take the binding rate p to be independent of force. A justification for this simplification is given in the ''Appendix''.…”

“…Experimentally, the interference issue was emphasized by the observation that unbinding of a motor in a twokinesin assembly is enhanced when both motors are bound to the microtubule. 53 While some modeling studied have reproduced this effect, 19,20,36 others have not or have in addition predicted a decrease of the velocity 41,61,64 that has not been observed. This confusing (theoretical) situation has led us to re-examine the case of two coupled motors.…”

“…38 This framework has been used to study unidirectional transport by one team of motors belonging to the same motor species 3,38 and was later extended to bidirectional transport by two teams of motors. [50][51][52] In addition, several groups have developed models that include detailed descriptions of the single motors involved and that address specific effects such as the stochasticity of stepping 19,41,42 and the geometry of motor assemblies. 13,20,21,40 As in the experimental studies listed above, the focus of recent theoretical work has been on assemblies of two motor molecules.…”

From the Cell Membrane to the Nucleus: Unearthing Transport Mechanisms for Dynein

“…Other authors model multiple motor based transport [13,29,30]. A paper by Mukherji [36] proposes a model for dynein by considering its mechanochemical cycle.…”