Drag racers and long haulers: the design space of myosin-V-like motor proteins

The ubiquitous myosin class-V molecular motors transport cellular cargo long distances at roughly 0.5 μm/s. Plant-specific myosin class-XI motors share nearly identical structural features with myosin-V, yet display velocities from 0.25 to 70 μm/s, the fastest transport motor in nature. Empirical observations suggest an inverse relationship between run length and velocity. These observations raise a central question: how can a single motor design support both highly processive "long-hauler" and extremely rapid "drag-racer" motors? We generalize a polymer-based model of force-dependent myosin-V dynamics to encompass the broader design space. The model quantitatively captures experimental data from fast myosin-XI and yields general analytical expressions for key observables. Notably, we derive a Pareto frontier that defines the trade-off between velocity and run distance, as well as the theoretical maximum velocity achievable by such motors. Our results establish the biological limits of natural and synthetic myosin-V-like motor design.

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Publication Details

Journal
bioRxiv (Cold Spring Harbor Laboratory)
Published
2026-10-27
DOI
https://doi.org/10.64898/2026.10.25.761746
Primary Topic
Microtubule and mitosis dynamics
Type
preprint

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preprint

Drag racers and long haulers: the design space of myosin-V-like motor proteins

Michael Hinczewski, Joshua B. Holmes
bioRxiv (Cold Spring Harbor Laboratory)
Microtubule and mitosis dynamics
preprint

Drag racers and long haulers: the design space of myosin-V-like motor proteins

Michael Hinczewski, Joshua B. Holmes
preprint en

Abstract

The ubiquitous myosin class-V molecular motors transport cellular cargo long distances at roughly 0.5 μm/s. Plant-specific myosin class-XI motors share nearly identical structural features with myosin-V, yet display velocities from 0.25 to 70 μm/s, the fastest transport motor in nature. Empirical observations suggest an inverse relationship between run length and velocity. These observations raise a central question: how can a single motor design support both highly processive "long-hauler" and extremely rapid "drag-racer" motors? We generalize a polymer-based model of force-dependent myosin-V dynamics to encompass the broader design space. The model quantitatively captures experimental data from fast myosin-XI and yields general analytical expressions for key observables. Notably, we derive a Pareto frontier that defines the trade-off between velocity and run distance, as well as the theoretical maximum velocity achievable by such motors. Our results establish the biological limits of natural and synthetic myosin-V-like motor design.

bioRxiv (Cold Spring Harbor Laboratory)
Case Western Reserve University (US)
Case Western Reserve University
Microtubule and mitosis dynamics
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