Pulling cargo increases the precision of molecular motor progress

Abstract

Biomolecular motors use free energy to drive a variety of cellular tasks, including the transport of cargo, such as vesicles and organelles. We find that the widely-used 'constant-force' approximation for the effect of cargo on motor dynamics leads to a much larger variance of motor step number compared to explicitly modeling diffusive cargo, suggesting the constant-force approximation may be misapplied in some cases. We also find that, with cargo, motor progress is significantly more precise than suggested by a recent result. For cargo with a low relative diffusivity, the dynamics of continuous cargo motion-rather than discrete motor steps-dominate, leading to a new, more permissive bound on the precision of motor progress which is independent of the number of stages per motor cycle.

Performance scaling and trade-offs for collective motor-driven transport

“…Similarly to D eff , φ decreases (and hence the precision increases) with the number of motors, scaling as φ ∝ N −1 . Here adding motors decreases the variance of forward progress while increasing the velocity, leading to a Fano factor that decreases with N. For N = 1 motor, equation ( 13) recovers the Fano factor previously calculated in the limit of low cargo diffusivity [24] for a single motor. The addition of motors can be thought of as having an 'averaging' effect on the dynamics.…”

“…We model each linker coupling one motor to the cargo as a Hookean spring with zero rest length, dominated by the along-filament displacement, thus with interaction potential U i (x c , 2 . This is a common assumption in modeling approaches [24,28] and experimentally well-supported for kinesin linkers [31].…”

“…The system stochasticity can alternatively be quantified by the coefficient of variation θ [39] or the Fano factor φ [24]. The coefficient of variation (CV) of cargo position is…”

“…These types of models assume that the motors pull against a constant force, rather than the stochastic frictional drag that would occur for a loosely coupled diffusive cargo. However, analysis of transport by single motors has shown that pulling a diffusing cargo and pulling against a constant force lead to qualitatively different transport behavior [23,24]. Researchers have proposed and explored several dynamical models for transport of diffusive cargo by multiple motors [25][26][27][28][29][30].…”

Theory of Nonequilibrium Free Energy Transduction by Molecular Machines

“…192 Conversely, simply adding a large (and hence slowly diffusing) towed cargo to a molecular motor [193][194][195] can considerably increase the achievable precision, because the effective number N of motor states is sensitive to strong coupling of the motor to its surroundings. 196 The thermodynamic uncertainty relation (28) can be applied widely, constraining heat engines in addition to isothermal motors, 197 and can be used to constrain other performance metrics, such as the efficiency of a molecular motor pulling against a constant force. 159 Beyond motors and machines, the thermodynamic uncertainty relation has been used to constrain molecular copying 198 and self-assembly processes.…”