"Cargo-mooring" as an operating principle for molecular motors

TL;DR

This paper proposes a new model for molecular motors that emphasizes cargo ratcheting over pulling, improving energy efficiency and accounting for environmental factors, with results aligning with experimental data.

Contribution

It introduces a cargo ratcheting mechanism for molecular motors, highlighting efficiency gains and environmental dependencies, advancing understanding of motor function.

Findings

Motor efficiency is increased by ratcheting rather than pulling.

Cargo size and medium viscosity significantly influence motor behavior.

Model aligns with experimental observations and offers new mechanistic insights.

Abstract

Routinely navigating through an ever-changing and unsteady environment, and utilizing chemical energy, molecular motors transport the cell's crucial components, such as neurotransmitters and organelles. They generate force and pull cargo, as they literally walk along the polymeric tracts, e.g. microtubules. However, using experimental data one may derive that the energy needed for this pulling would take the most part of the 22 kT that ATP hydrolysis makes available. In such a case there would not be sufficient energy left to drive the conformational changes in the catalytic cycle of the protein. Furthermore, the medium inside living cell is viscoelastic. Pulling cargo in such an environment takes more energy than in aqueous buffer solution. Here we propose a mechanism for the motor to more efficiently utilize chemical energy. In our model the energy is used to ratchet the cargo forward. The motor no longer pulls, but only holds a bead or a vesicle, allowing for Brownian motion in a range limited by the elasticity of the motor-cargo-track system. The consequence of such a mechanism is the dependency of motion not only on the motor, but also on the cargo (especially it's size) and on the environment (i.e. it's viscosity and structure). However, current experimental works rarely provide this type of information for in vivo studies. We suggest that even small differences between assays can impact the outcome. Our results agree with those obtained in wet laboratories and provide novel insight in the mechanism of a molecular motor's functioning.