Mechanical coordination in motor ensembles revealed using engineered artificial myosin filaments

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Abstract

The sarcomere of muscle is composed of tens of thousands of myosin motors that self-assemble into thick filaments and interact with surrounding actin-based thin filaments in a dense, near-crystalline hexagonal lattice1. Together, these actin–myosin interactions enable large-scale movement and force generation, two primary attributes of muscle. Research on isolated fibres has provided considerable insight into the collective properties of muscle, but how actin–myosin interactions are coordinated in an ensemble remains poorly understood2. Here, we show that artificial myosin filaments, engineered using a DNA nanotube scaffold, provide precise control over motor number, type and spacing. Using both dimeric myosin V- and myosin VI-labelled nanotubes, we find that neither myosin density nor spacing has a significant effect on the gliding speed of actin filaments. This observation supports a simple model of myosin ensembles as energy reservoirs that buffer individual stochastic events to bring about smooth, continuous motion. Furthermore, gliding speed increases with cross-bridge compliance, but is limited by Brownian effects. As a first step to reconstituting muscle motility, we demonstrate human β-cardiac myosin-driven gliding of actin filaments on DNA nanotubes.

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Figure 1: Formation of synthetic myosin filaments using DNA nanotubes.
Figure 2: Density and number of myosins on synthetic filaments have negligible effect on gliding speeds.
Figure 3: Stochastic simulation of actin gliding along myosin filaments predicts actin length-independent gliding speed for sufficiently high motor number.
Figure 4: Actin gliding on synthetic human β-cardiac myosin filaments.

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Acknowledgements

The authors thank M. Westfall, D. Smith and L. Hilbert for useful discussions. Research was funded by the American Heart Association Scientist Development Grant (13SDG14270009), National Institutes of Health (NIH) grants 1DP2 CA186752-01 and 1-R01-GM-105646-01-A1 to S.S. and NIH grants GM33289 and HL117138 to J.A.S. R.F.S. is a Life Sciences Research Foundation Fellow. R.E.T. is supported by the NIH (F32 HL123247-02) and A.S.A. is supported by a Lucile Packard CHRI Postdoctoral Award.

Author information

R.F.H., R.F.S., A.S.A., R.E.T., J.A.S. and S.S. planned and designed experiments. R.F.H., R.F.S., A.S.A., R.E.T. and S.Su. performed experiments and analysed the results. R.F.H. and S.S. performed the mathematical modelling. R.F.H., R.F.S., J.A.S. and S.S. wrote the manuscript.

Correspondence to S. Sivaramakrishnan.

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Hariadi, R., Sommese, R., Adhikari, A. et al. Mechanical coordination in motor ensembles revealed using engineered artificial myosin filaments. Nature Nanotech 10, 696–700 (2015) doi:10.1038/nnano.2015.132

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