1. Physics of Living Systems
  2. Structural Biology and Molecular Biophysics
Download icon

Myosin V executes steps of variable length via structurally constrained diffusion

  1. David Hathcock  Is a corresponding author
  2. Riina Tehver
  3. Michael Hinczewski  Is a corresponding author
  4. Dave Thirumalai
  1. Cornell University, United States
  2. Denison University, United States
  3. Case Western Reserve University, United States
  4. University of Texas, Austin, United States
Research Article
  • Cited 2
  • Views 1,432
  • Annotations
Cite this article as: eLife 2020;9:e51569 doi: 10.7554/eLife.51569


The molecular motor myosin V transports cargo by stepping on actin filaments, executing a random diffusive search for actin binding sites at each step. A recent experiment suggests that the joint between the myosin lever arms may not rotate freely, as assumed in earlier studies, but instead has a preferred angle giving rise to structurally constrained diffusion. We address this controversy through comprehensive analytical and numerical modeling of myosin V diffusion and stepping. When the joint is constrained, our model reproduces the experimentally observed diffusion, allowing us to estimate bounds on the constraint energy. We also test the consistency between the constrained diffusion model and previous measurements of step size distributions and the load dependence of various observable quantities. The theory lets us address the biological significance of the constrained joint and provides testable predictions of new myosin behaviors, including the stomp distribution and the run length under off-axis force.

Data availability

All the data for the figures in the study (Fig. 3-8), along with the corresponding code to process the data and produce the figures, is included in the source data file uploaded with the submission.

Article and author information

Author details

  1. David Hathcock

    Department of Physics, Cornell University, Ithaca, United States
    For correspondence
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4551-9239
  2. Riina Tehver

    Department of Physics and Astronomy, Denison University, Granville, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Michael Hinczewski

    Department of Physics, Case Western Reserve University, Cleveland, United States
    For correspondence
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2837-7697
  4. Dave Thirumalai

    Department of Chemistry, University of Texas, Austin, Austin, United States
    Competing interests
    The authors declare that no competing interests exist.


National Science Foundation (DGE-1650441)

  • David Hathcock

National Science Foundation (CHE 19-00033)

  • Dave Thirumalai

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Taekjip Ha, Johns Hopkins University, United States

Publication history

  1. Received: September 3, 2019
  2. Accepted: January 14, 2020
  3. Accepted Manuscript published: January 15, 2020 (version 1)
  4. Version of Record published: March 3, 2020 (version 2)


© 2020, Hathcock et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.


  • 1,432
    Page views
  • 186
  • 2

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Physics of Living Systems
    Osman Darici, Arthur D Kuo
    Research Article

    The simple task of walking up a sidewalk curb is actually a dynamic prediction task. The curb is a disturbance that could cause a loss of momentum if not anticipated and compensated for. It might be possible to adjust momentum sufficiently to ensure undisturbed time of arrival, but there are infinite possible ways to do so. Much of steady, level gait is determined by energy economy, which should be at least as important with terrain disturbances. It is, however, unknown whether economy also governs walking up a curb, and whether anticipation helps. Here we show that humans compensate with an anticipatory pattern of forward speed adjustments, predicted by a criterion of minimizing mechanical energy input. The strategy is mechanistically predicted by optimal control for a simple model of bipedal walking dynamics, with each leg's push-off work as input. Optimization predicts a tri-phasic trajectory of speed (and thus momentum) adjustments, including an anticipatory phase. In experiment, human subjects ascend an artificial curb with the predicted tri-phasic trajectory, which approximately conserves overall walking speed relative to undisturbed flat ground. The trajectory involves speeding up in a few steps before the curb, losing considerable momentum from ascending it, and then regaining speed in a few steps thereafter. Descending the curb entails a nearly opposite, but still anticipatory, speed fluctuation trajectory, in agreement with model predictions that speed fluctuation amplitudes should scale linearly with curb height. The fluctuation amplitudes also decrease slightly with faster average speeds, also as predicted by model. Humans can reason about the dynamics of walking to plan anticipatory and economical control, even with a sidewalk curb in the way.

    1. Cell Biology
    2. Physics of Living Systems
    Raimund Schlüßler et al.
    Research Article

    Quantitative measurements of physical parameters become increasingly important for understanding biological processes. Brillouin microscopy (BM) has recently emerged as one technique providing the 3D distribution of viscoelastic properties inside biological samples - so far relying on the implicit assumption that refractive index (RI) and density can be neglected. Here, we present a novel method (FOB microscopy) combining BM with optical diffraction tomography and epi-fluorescence imaging for explicitly measuring the Brillouin shift, RI and absolute density with specificity to fluorescently labeled structures. We show that neglecting the RI and density might lead to erroneous conclusions. Investigating the nucleoplasm of wild-type HeLa cells, we find that it has lower density but higher longitudinal modulus than the cytoplasm. Thus, the longitudinal modulus is not merely sensitive to the water content of the sample - a postulate vividly discussed in the field. We demonstrate the further utility of FOB on various biological systems including adipocytes and intracellular membraneless compartments. FOB microscopy can provide unexpected scientific discoveries and shed quantitative light on processes such as phase separation and transition inside living cells.