Processivity of molecular motors under vectorial loads

Abstract

Molecular motors are cellular machines that drive the spatial organization of the cells by transporting cargoes along intracellular filaments. Although the mechanical properties of single molecular motors are relatively well characterised, it remains elusive how the three-dimensional geometry of a load imposed on a motor affects its processivity, i.e., the average distance that a motor moves per interaction with a filament. Here, we theoretically explore this question for a single kinesin molecular motor by analysing the load-dependence of the stepping and detachment processes. We find that the processivity of kinesin increases with lowering the load angle between kinesin and microtubule, due to the deceleration of the detachment rate. When the load angle is large, it is predicted that processivity can be enhanced if the velocity becomes less sensitive to load, through an optimal distribution of the load over the kinetic transition rates underlying a mechanical step of the motor. These results provide new insights into understanding of the design of potential synthetic biomolecular machines that can travel long distances with high velocities.

Highly-parallel microfluidics-based force spectroscopy on single cytoskeletal motors

“…The overall higher interaction times observed under resisting loads, as compared to assisting loads, suggest that kinesin-1 exhibits a higher detachment rate under assisting loads. This is in agreement with the higher unbinding force observed for kinesin-1 under resisting load as compared to assisting load 38 and with the theoretical prediction that horizontal forces alone, as predominantly present in our setup, decelerate motor detachment 35,36 . The mean interaction times obtained for both assisting and resisting loads, correspond well to the interaction time of 0.95 s under unloaded conditions reported previously for the kinesin-1 at room temperature 33 .…”

“…The overall higher interaction times observed under resisting loads, as compared to assisting loads, suggest that kinesin-1 exhibits a higher detachment rate under assisting loads. This is in agreement with the higher unbinding force observed for kinesin-1 under resisting load as compared to assisting load 32 and with the theoretical prediction that horizontal forces alone, as predominantly present in our setup, decelerate motor detachment 33,34 Our hydrodynamic force assay not only enables parallelization of the measurements on cytoskeletal motors, but also provides an alternative geometry of force application compared to existing methods. While optical traps-the method of choice for characterizing cytoskeletal motors-have been exploited to study the application of forward, backward 29,31,35 , and sideward loads 28,36 on stepping kinesins using a variety of geometries 37,38 , they generally suffer from a poor control over vertically applied forces, which may bias the measurements performed [39][40][41][42] .…”