Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Controlling load-dependent kinetics of β-cardiac myosin at the single-molecule level

Abstract

Concepts in molecular tension sensing in biology are growing and have their origins in studies of muscle contraction. In the heart muscle, a key parameter of contractility is the detachment rate of myosin from actin, which determines the time that myosin is bound to actin in a force-producing state and, importantly, depends on the load (force) against which myosin works. Here we measure the detachment rate of single molecules of human β-cardiac myosin and its load dependence. We find that both can be modulated by both small-molecule compounds and cardiomyopathy-causing mutations. Furthermore, effects of mutations can be reversed by introducing appropriate compounds. Our results suggest that activating versus inhibitory perturbations of cardiac myosin are discriminated by the aggregate result on duty ratio, average force, and ultimately average power output and suggest that cardiac contractility can be controlled by tuning the load-dependent kinetics of single myosin molecules.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Load-dependent kinetics of single molecules of human β-cardiac myosin measured by HFS.
Fig. 2: Dose-dependent effects of small-molecule compounds on the actin-sliding velocity of β-cardiac myosin in unloaded, in vitro motility.
Fig. 3: Effects of small-molecule compounds on the load-dependent kinetics of single molecules of β-cardiac myosin.
Fig. 4: Effects of cardiomyopathy-causing mutations on the load-dependent kinetics of single molecules of β-cardiac myosin, and their reversal by small-molecule compounds.
Fig. 5: Dosage analysis of OM’s effect on the load-dependent detachment kinetics of single molecules of β-cardiac myosin.
Fig. 6: Single-molecule load-dependent kinetics as the basis of the ensemble force–velocity relationship in β-cardiac myosin.
Fig. 7: The effects of small-molecule compounds and cardiomyopathy-causing mutations on the power produced by single molecules of β-cardiac myosin.
Fig. 8: Predictions of the effects of small-molecule compounds and cardiomyopathy-causing mutations on the contractility of β-cardiac myosin at the single molecule level.

References

  1. Petridou, N. I., Spiró, Z. & Heisenberg, C. P. Multiscale force sensing in development. Nat. Cell Biol. 19, 581–588 (2017).

    Article  PubMed  CAS  Google Scholar 

  2. Malinova, T. S. & Huveneers, S. Sensing of cytoskeletal forces by asymmetric adherens junctions. Trends Cell Biol. 28, 328–341 (2018).

    Article  PubMed  CAS  Google Scholar 

  3. Roca-Cusachs, P., Conte, V. & Trepat, X. Quantifying forces in cell biology. Nat. Cell Biol. 19, 742–751 (2017).

    Article  PubMed  CAS  Google Scholar 

  4. Ribeiro, A. J. et al. Contractility of single cardiomyocytes differentiated from pluripotent stem cells depends on physiological shape and substrate stiffness. Proc. Natl. Acad. Sci. USA 112, 12705–12710 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Huang, D. L., Bax, N. A., Buckley, C. D., Weis, W. I. & Dunn, A. R. Vinculin forms a directionally asymmetric catch bond with F-actin. Science 357, 703–706 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Buckley, C. D. et al. Cell adhesion. The minimal cadherin-catenin complex binds to actin filaments under force. Science 346, 1254211 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Altman, D., Sweeney, H. L. & Spudich, J. A. The mechanism of myosin VI translocation and its load-induced anchoring. Cell 116, 737–749 (2004).

    Article  PubMed  CAS  Google Scholar 

  8. Purcell, T. J., Sweeney, H. L. & Spudich, J. A. A force-dependent state controls the coordination of processive myosin V. Proc. Natl. Acad. Sci. USA 102, 13873–13878 (2005).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Fenn, W. O. A quantitative comparison between the energy liberated and the work performed by the isolated sartorius muscle of the frog. J. Physiol. (Lond.) 58, 175–203 (1923).

    Article  CAS  Google Scholar 

  10. Greenberg, M. J., Shuman, H. & Ostap, E. M. Inherent force-dependent properties of β-cardiac myosin contribute to the force-velocity relationship of cardiac muscle. Biophys. J. 107, L41–L44 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Sung, J. et al. Harmonic force spectroscopy measures load-dependent kinetics of individual human β-cardiac myosin molecules. Nat. Commun. 6, 7931 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Capitanio, M. et al. Ultrafast force-clamp spectroscopy of single molecules reveals load dependence of myosin working stroke. Nat. Methods 9, 1013–1019 (2012).

    Article  PubMed  CAS  Google Scholar 

  13. Veigel, C., Molloy, J. E., Schmitz, S. & Kendrick-Jones, J. Load-dependent kinetics of force production by smooth muscle myosin measured with optical tweezers. Nat. Cell Biol. 5, 980–986 (2003).

    Article  PubMed  CAS  Google Scholar 

  14. Veigel, C., Schmitz, S., Wang, F. & Sellers, J. R. Load-dependent kinetics of myosin-V can explain its high processivity. Nat. Cell Biol. 7, 861–869 (2005).

    Article  PubMed  CAS  Google Scholar 

  15. Laakso, J. M., Lewis, J. H., Shuman, H. & Ostap, E. M. Myosin I can act as a molecular force sensor. Science 321, 133–136 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Greenberg, M. J., Lin, T., Goldman, Y. E., Shuman, H. & Ostap, E. M. Myosin IC generates power over a range of loads via a new tension-sensing mechanism. Proc. Natl. Acad. Sci. USA 109, E2433–E2440 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  17. Nyitrai, M. et al. What limits the velocity of fast-skeletal muscle contraction in mammals? J. Mol. Biol. 355, 432–442 (2006).

    Article  PubMed  CAS  Google Scholar 

  18. Weiss, S., Rossi, R., Pellegrino, M. A., Bottinelli, R. & Geeves, M. A. Differing ADP release rates from myosin heavy chain isoforms define the shortening velocity of skeletal muscle fibers. J. Biol. Chem. 276, 45902–45908 (2001).

    Article  PubMed  CAS  Google Scholar 

  19. Capitanio, M. et al. Two independent mechanical events in the interaction cycle of skeletal muscle myosin with actin. Proc. Natl. Acad. Sci. USA 103, 87–92 (2006).

    Article  PubMed  CAS  Google Scholar 

  20. Aksel, T., Choe, Yu,E., Sutton, S., Ruppel, K. M. & Spudich, J. A. Ensemble force changes that result from human cardiac myosin mutations and a small-molecule effector. Cell Rep. 11, 910–920 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Reiser, P. J., Portman, M. A., Ning, X. H. & Schomisch Moravec, C. Human cardiac myosin heavy chain isoforms in fetal and failing adult atria and ventricles. Am. J. Physiol. Heart Circ. Physiol. 280, H1814–H1820 (2001).

    Article  PubMed  CAS  Google Scholar 

  22. Krenz, M. & Robbins, J. Impact of beta-myosin heavy chain expression on cardiac function during stress. J. Am. Coll. Cardiol. 44, 2390–2397 (2004).

    Article  PubMed  CAS  Google Scholar 

  23. Malik, F. I. et al. Cardiac myosin activation: a potential therapeutic approach for systolic heart failure. Science 331, 1439–1443 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Kadota, S. et al. Ribonucleotide reductase-mediated increase in dATP improves cardiac performance via myosin activation in a large animal model of heart failure. Eur. J. Heart Fail. 17, 772–781 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Regnier, M., Rivera, A. J., Chen, Y. & Chase, P. B. 2-deoxy-ATP enhances contractility of rat cardiac muscle. Circ. Res. 86, 1211–1217 (2000).

    Article  PubMed  CAS  Google Scholar 

  26. Takagi, Y., Homsher, E. E., Goldman, Y. E. & Shuman, H. Force generation in single conventional actomyosin complexes under high dynamic load. Biophys. J. 90, 1295–1307 (2006).

    Article  PubMed  CAS  Google Scholar 

  27. Teerlink, J. R. et al. Chronic oral study of myosin activation to increase contractility in heart failure (COSMIC-HF): a phase 2, pharmacokinetic, randomised, placebo-controlled trial. Lancet 388, 2895–2903 (2016).

    Article  PubMed  CAS  Google Scholar 

  28. Liu, Y., White, H. D., Belknap, B., Winkelmann, D. A. & Forgacs, E. Omecamtiv mecarbil modulates the kinetic and motile properties of porcine β-cardiac myosin. Biochemistry 54, 1963–1975 (2015).

    Article  PubMed  CAS  Google Scholar 

  29. Swenson, A. M. et al. Omecamtiv mecarbil enhances the duty ratio of human β-cardiac myosin resulting in increased calcium sensitivity and slowed force development in cardiac muscle. J. Biol. Chem. 292, 3768–3778 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Rohde, J. A., Thomas, D. D. & Muretta, J. M. Heart failure drug changes the mechanoenzymology of the cardiac myosin powerstroke. Proc. Natl. Acad. Sci. USA 114, E1796–E1804 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Kron, S. J., Uyeda, T. Q., Warrick, H. M. & Spudich, J. A. An approach to reconstituting motility of single myosin molecules. J. Cell Sci. Suppl. 14, 129–133 (1991).

    Article  PubMed  CAS  Google Scholar 

  32. Adhikari, A. S. et al. Early-onset hypertrophic cardiomyopathy mutations significantly increase the velocity, force, and actin-activated ATPase activity of human β-cardiac myosin. Cell Rep. 17, 2857–2864 (2016).

    Article  PubMed  CAS  Google Scholar 

  33. Hastings, J.W., Gibson, Q.H., Friedland, J. & Spudich, J.A. in Bioluminescence in Progress (eds. Johnson, F.H. & Haneda, Y.) 151–186 (Princeton University Press, Princeton, NJ, 1966).

  34. Woody, M. S., Lewis, J. H., Greenberg, M. J., Goldman, Y. E. & Ostap, E. M. MEMLET: an easy-to-use tool for data fitting and model comparison using maximum-likelihood estimation. Biophys. J. 111, 273–282 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Planelles-Herrero, V. J., Hartman, J. J., Robert-Paganin, J., Malik, F. I. & Houdusse, A. Mechanistic and structural basis for activation of cardiac myosin force production by omecamtiv mecarbil. Nat. Commun. 8, 190 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Uyeda, T. Q., Kron, S. J. & Spudich, J. A. Myosin step size. Estimation from slow sliding movement of actin over low densities of heavy meromyosin. J. Mol. Biol. 214, 699–710 (1990).

    Article  PubMed  CAS  Google Scholar 

  37. Brizendine, R. K. et al. A mixed-kinetic model describes unloaded velocities of smooth, skeletal, and cardiac muscle myosin filaments in vitro. Sci. Adv. 3, o2267 (2017).

    Article  Google Scholar 

  38. Sommese, R. F. et al. Molecular consequences of the R453C hypertrophic cardiomyopathy mutation on human β-cardiac myosin motor function. Proc. Natl. Acad. Sci. USA 110, 12607–12612 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  39. Nag, S. et al. Contractility parameters of human β-cardiac myosin with the hypertrophic cardiomyopathy mutation R403Q show loss of motor function. Sci. Adv. 1, e1500511 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Walcott, S., Warshaw, D. M. & Debold, E. P. Mechanical coupling between myosin molecules causes differences between ensemble and single-molecule measurements. Biophys. J. 103, 501–510 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Liu, C., Kawana, M., Song, D., Ruppel, K.M. & Spudich, J. Controlling load-dependent contractility of the heart at the single molecule level. bioRxiv https://doi.org/10.1101/258020 (2018).

  42. Woody, M. S. et al. Positive cardiac inotrope, omecamtiv mecarbil, activates muscle despite suppressing the myosin working stroke. bioRxiv https://doi.org/10.1101/298141 (2018).

    Article  Google Scholar 

  43. Ho, C. Y. et al. Assessment of diastolic function with Doppler tissue imaging to predict genotype in preclinical hypertrophic cardiomyopathy. Circulation 105, 2992–2997 (2002).

    Article  PubMed  Google Scholar 

  44. Ujfalusi, Z. et al. Dilated cardiomyopathy myosin mutants have reduced force-generating capacity. J. Biol. Chem. jbc.RA118.001938 (2018).

  45. Tang, W. et al. Modulating beta-cardiac myosin function at the molecular and tissue levels. Front. Physiol. 7, 659 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  46. Kampourakis, T., Zhang, X., Sun, Y. B. & Irving, M. Omecamtiv mercabil and blebbistatin modulate cardiac contractility by perturbing the regulatory state of the myosin filament. J. Physiol. (Lond.) 596, 31–46 (2018).

    Article  CAS  Google Scholar 

  47. Linari, M. et al. Force generation by skeletal muscle is controlled by mechanosensing in myosin filaments. Nature 528, 276–279 (2015).

    Article  PubMed  CAS  Google Scholar 

  48. Spudich, J. A. The myosin mesa and a possible unifying hypothesis for the molecular basis of human hypertrophic cardiomyopathy. Biochem. Soc. Trans. 43, 64–72 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Nag, S. et al. The myosin mesa and the basis of hypercontractility caused by hypertrophic cardiomyopathy mutations. Nat. Struct. Mol. Biol. 24, 525–533 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Trivedi, D. V., Adhikari, A. S., Sarkar, S. S., Ruppel, K. M. & Spudich, J. A. Hypertrophic cardiomyopathy and the myosin mesa: viewing an old disease in a new light. Biophys. Rev. 10, 27–48 (2018).

    Article  PubMed  CAS  Google Scholar 

  51. Anderson, R.L. et al. Mavacamten stabilizes a folded-back sequestered super-relaxed state of β-cardiac myosin. bioRxiv https://doi.org/10.1101/266783 (2018).

  52. Rohde, J.A., Thomas, D.D. & Muretta, J.M. Mavacamten stabilizes the auto-inhibited state of two-headed cardiac myosin. bioRxiv https://doi.org/10.1101/287425 (2018).

  53. Kawana, M., Sarkar, S. S., Sutton, S., Ruppel, K. M. & Spudich, J. A. Biophysical properties of human β-cardiac myosin with converter mutations that cause hypertrophic cardiomyopathy. Sci. Adv. 3, e1601959 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  54. Trybus, K. M. Biochemical studies of myosin. Methods 22, 327–335 (2000).

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The authors thank all members of the Spudich lab, J. Sung, S. Nag, and R. McDowell for discussions and edits to the manuscript; D. Herschlag, C. Limouse, and S. Bonilla for discussions on the data analysis and interpretation; M. Woody for discussions on OM and help with MEMLET; J. Baker for discussions on attachment vs. detachment rate-limited motility velocity; and F. Malik and J. Hartman for discussions on clinically relevant dosage of OM. We thank MyoKardia, Inc., for providing the various small-molecule effectors of the human β-cardiac myosin that were derived from their screens, as well as dATP and bovine actin. This work was funded by NIH grants RO1GM033289 (J.A.S.), RO1HL117138 (J.A.S.), T32GM007276 (C.L.), TL1RR025742 (C.L.), and F32HL124883 (M.K.); a Stanford Bio-X fellowship (C.L.); and Stanford School of Medicine Dean’s Postdoctoral Fellowship (D.S.). The content is solely the responsibility of the authors and does not necessarily represent the official view of the National Institutes of Health.

Author information

Authors and Affiliations

Authors

Contributions

C.L. performed single molecule experiments and analyzed the data. M.K. performed in vitro motility experiments and analyzed the data. C.L. and D.S. performed ATPase experiments. D.S. analyzed the ATPase data. M.K., D.S., and K.M.R. expressed and purified protein. C.L. and J.A.S. wrote the paper. All authors discussed the data as they evolved and reviewed and edited the paper.

Corresponding authors

Correspondence to Chao Liu or James A. Spudich.

Ethics declarations

Competing interests

J.A.S. is a founder of Cytokinetics, Inc., and MyoKardia, Inc., is a member of their advisory boards, and owns shares in the companies. K.M.R. is a member of the MyoKardia scientific advisory board.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Integrated Supplementary Information

Supplementary Figure 1 Purified actin and myosin shown by SDS-PAGE.

Lane 1: bovine cardiac actin (MW = 42 kDa) used in the actin-activated ATPase assay. Lane 2: recombinant human β-cardiac myosin sS1 (residues 1-808) fused to a C-terminal eGFP that migrates around 120 kDa. Myosin sS1 fragment was co-purified with a FLAG-tagged human ventricular essential light chain in which the FLAG tag had been cleaved off by TEV protease and migrates around 22 kDa.

Supplementary Figure 2 Example molecule from each condition measured (part 1).

Event lifetimes are plotted against load force (top). The detachment rate k det at each force is determined by MLE on the exponentially-distributed lifetimes. k det is then fitted to the Arrhenius equation with harmonic force correction (Eqn. 1) (bottom). An example of WT without compound is shown in Fig. 1c,d. Error bars are calculated as the variance on the MLE from the inverse Fisher information matrix.

Supplementary Figure 3 Example molecule from each condition measured (part 2).

Event lifetimes are plotted against load force (top). The detachment rate k det at each force is determined by MLE on the exponentially-distributed lifetimes. k det is then fitted to the Arrhenius equation with harmonic force correction (Eqn. 1) (bottom). An example of WT without compound is shown in Fig. 1c-d. Error bars are calculated as the variance on the MLE from the inverse Fisher information matrix.

Supplementary Figure 4 Effects of small-molecule compounds on the load-dependent kinetics of single molecules of human β-cardiac myosin.

Each gray line represents one molecule fitted to k det from events binned by force, shown as data points without error bars for clarity. The weighted means of k 0 and δ across molecules for each condition have a curve represented in black and also plotted in Fig. 3b. Their values are given in Table 1 and Supplementary Table 1. The plot for WT is replicated from Fig. 1f for comparison. In the case of dATP, 2 mM dATP was used in place of ATP. All other conditions used 2 mM ATP, 2% DMSO, and 25 µM compound.

Supplementary Figure 5 Effects of cardiomyopathy-causing mutations on the load-dependent kinetics of single molecules of human β-cardiac myosin, and their reversal by small-molecule compounds.

Each thin line represents one molecule fitted to k det from events binned by force, shown as data points without error bars for clarity. The weighted means of k 0 and δ across molecules for each condition have a curve represented as a thick line and also plotted in Fig. 4b. Their values are given in Table 1 and Supplementary Table 1. Addition of 25 µM compound F3345 to D239N and H251N and OM to R237W were in the presence of 2% DMSO, therefore effects of 2% DMSO (blue) on these mutants were also measured. Mutant A223T had no significant change from WT, therefore no compounds were added. The plot for WT is replicated from Fig. 1f for comparison.

Supplementary Figure 6 Effects of small-molecule compounds and cardiomyopathy-causing mutations on the load-dependent kinetics of single β-cardiac myosin molecules.

The weighted average detachment rate curves for the different conditions are replicated from Fig. 3 and 4. Their k 0 and δ values are given in Table 1. Black: WT. Gray: DMSO. Blue: HCM or activators. Red: DCM or inhibitor.

Supplementary Figure 7 Durations of all events in the F = 0 force bin from all molecules for each condition measured.

For each condition, the red curve represents the single exponential distribution parameterized by a single detachment rate. Even at the saturating 25 µM concentration of OM, there are still two populations better described by a double (green) rather than a single (red) exponential distribution (top). F ≠ 0 bins show similar single (all conditions except OM) or double (OM) exponential distributions (not shown).

Supplementary Figure 8 Unloaded actin-sliding velocities measured by in vitro motility assay vs. the attachment rate, kattach.

Linear regression gives R2 = 0.35. Motility velocity of mutants and dATP are obtained from other studies (Aksel, T., Choe Yu, E., Sutton, S., Ruppel, K. M. & Spudich, J. A. Ensemble force changes that result from human cardiac myosin mutations and a small-molecule effector. Cell Rep 11, 910-920, doi:10.1016/j.celrep.2015.04.006 (2015); Regnier, M., Rivera, A. J., Chen, Y. & Chase, P. B. 2-deoxy-ATP enhances contractility of rat cardiac muscle. Circ Res 86, 1211-1217 (2000); Adhikari, A. S. et al. Early-Onset Hypertrophic Cardiomyopathy Mutations Significantly Increase the Velocity, Force, and Actin-Activated ATPase Activity of Human beta-Cardiac Myosin. Cell Rep 17, 2857-2864, doi:10.1016/j.celrep.2016.11.040 (2016); Ujfalusi, Z. et al. Dilated cardiomyopathy myosin mutants have reduced force-generating capacity. J Biol Chem, doi:10.1074/jbc.RA118.001938 (2018); Tomasic I., Liu C., Rodriguez H., Spudich J.A., Bartholomew Ingle S.R., manuscript in preparation). Horizontal error bars are propagated errors from the k attach calculation. Vertical error bars are s.e.m. (see Methods).

Supplementary Figure 9 Effects of compounds on the actin-sliding velocities of human β-cardiac myosin in the loaded in vitro motility.

a, Percent time mobile (a measure of velocity) as a function of the actin-binding protein utrophin, which served as a resistive load against myosin in the motility assay, at different concentrations of compound. Error bars represent s.e.m. of bootstrapped data calculated by the FAST program (Aksel, T., Choe Yu, E., Sutton, S., Ruppel, K. M. & Spudich, J. A. Ensemble force changes that result from human cardiac myosin mutations and a small-molecule effector. Cell Rep 11, 910-920, doi:10.1016/j.celrep.2015.04.006 (2015)). Dashed lines denote K s , a measure of the ensemble load-bearing ability of myosin. K s roughly corresponds to the concentration of utrophin required to slow down velocity by half (see Aksel et al. Cell Rep 2015 for rigorous definition). b, K s from (a) is plotted against compound concentration. Error bars represent s.e.m.

Supplementary Figure 10 Effects of compounds on the actin-activated ATPase of human β-cardiac myosin.

a, The Michaelis-Menten equation fitted to ATPase data for all conditions performed with one protein preparation. The entire experiment measuring all conditions was done on the same day that the protein was purified. Error bars on data points are s.e.m. of replicate experiments (N = 3 in this example). Errors on k cat and K m are estimated fitting errors. k cat ’s from each day’s experiment are averaged to calculate the mean and s.e.m. given in Table 1. b, The Michaelis-Menten equation fitted to ATPase data aggregated from both protein preparations. Here, error bars on data points are s.e.m. of all replicates (total 5 - 7), and errors on k cat and K m are estimated fitting errors.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, C., Kawana, M., Song, D. et al. Controlling load-dependent kinetics of β-cardiac myosin at the single-molecule level. Nat Struct Mol Biol 25, 505–514 (2018). https://doi.org/10.1038/s41594-018-0069-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41594-018-0069-x

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing