Productive Cooperation among Processive Motors Depends Inversely on Their Mechanochemical Efficiency

Abstract

Subcellular cargos are often transported by teams of processive molecular motors, which raises questions regarding the role of motor cooperation in intracellular transport. Although our ability to characterize the transport behaviors of multiple-motor systems has improved substantially, many aspects of multiple-motor dynamics are poorly understood. This work describes a transition rate model that predicts the load-dependent transport behaviors of multiple-motor complexes from detailed measurements of a single motor's elastic and mechanochemical properties. Transition rates are parameterized via analyses of single-motor stepping behaviors, load-rate-dependent motor-filament detachment kinetics, and strain-induced stiffening of motor-cargo linkages. The model reproduces key signatures found in optical trapping studies of structurally defined complexes composed of two kinesin motors, and predicts that multiple kinesins generally have difficulties in cooperating together. Although such behavior is influenced by the spatiotemporal dependence of the applied load, it appears to be directly linked to the efficiency of kinesin's stepping mechanism, and other types of less efficient and weaker processive motors are predicted to cooperate more productively. Thus, the mechanochemical efficiencies of different motor types may determine how effectively they cooperate together, and hence how motor copy number contributes to the regulation of cargo motion.

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''.…”

“…Other more complicated approaches have been discussed in several studies. 19,20,35,48 Our approach is based on the observation that binding and unbinding proceed along different pathways: whereas unbinding dominantly occurs from strained configurations (all states (2,i) with i > 0), motors mostly bind in a relaxed configuration, i. e. to state (2,0). Therefore, we describe binding with a single rate that is independent of the force.…”

“…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.…”

“…[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. In particular, several recent studies have addressed the model case of two coupled kinesin-1 motors.…”