Collective Force Generation by Molecular Motors Is Determined by Strain-Induced Unbinding

Abstract

In the living cell, we encounter a large variety of motile processes such as organelle transport and cytoskeleton remodeling. These processes are driven by motor proteins that generate force by transducing chemical free energy into mechanical work. In many cases, the molecular motors work in teams to collectively generate larger forces. Recent optical trapping experiments on small teams of cytoskeletal motors indicated that the collectively generated force increases with the size of the motor team but that this increase depends on the motor type and on whether the motors are studied in vitro or in vivo. Here, we use the theory of stochastic processes to describe the motion of N motors in a stationary optical trap and to compute the Ndependence of the collectively generated forces. We consider six distinct motor types, two kinesins, two dyneins, and two myosins. We show that the force increases always linearly with N but with a prefactor that depends on the performance of the single motor. Surprisingly, this prefactor increases for weaker motors with a lower stall force. This counter-intuitive behavior reflects the increased probability with which stronger motors detach from the filament during strain generation. Our theoretical results are in quantitative agreement with experimental data on small teams of kinesin-1 motors.

Cross-linkers at growing microtubule ends generate forces that drive actin transport

“…Within the cell, the condensation force we identified will compete with forces exerted by molecular motors. We showed that actin transport by growing microtubule plus-ends results in much lower forces (0.10 pN) than are measured for microtubule motor proteins (1 pN to 10 pN) [39,40]. In direct competition, motor forces would therefore likely dominate over the condensation forces.…”

“…Actin transport by growing microtubule plus ends results in much lower forces than are measured for microtubule motor proteins 0.10 pN for microtubule growth compared to 1-10 pN for single motors or collectives of motor proteins) [33, 34]. In direct competition, motor forces would therefore likely dominate over the condensation forces.…”

Velocity of myosin-based actin sliding depends on attachment and detachment kinetics and reaches a maximum when myosin-binding sites on actin saturate

“…Optical traps and in vitro motility experiments have been used to study how force and motion generation change with increasing numbers, N, of motors (9)(10)(11) and in general show that the mechanics of many motors working together is not a simple sum of the molecular mechanics of individual motors (4,12,13). Consistent with the chemical thermodynamic model that we first proposed over 20 years ago (14), many studies now indicate that force is collectivelygenerated and thermally-distributed within systems of motors (12,13,15). This leads to emergent mechanochemical properties (12,13,16) that are more accurately described by the thermodynamics of a motor ensemble than by molecular mechanics (14,17,18).…”

Modelling cytoskeletal transport by clusters of non-processive molecular motors with limited binding sites

“…A natural extension to our work would be to include force dependence in the unbinding rate k off as has been done in [ 1 , 14 , 51 ] and recently by Ucar & Lipowsky [ 71 ]. We would expect that including this effect would increase the force sensitivity, increase the time taken to reach steady state, decrease the stall force and decrease the mean velocity due to the zipper effect of successive leading motors experiencing the force-dependent unbinding.…”