title: Mechanical coordination in motor ensembles revealed using engineered artificial myosin filaments.
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 lattice. 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 understood. 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.
authors.affiliation: Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: R F
authors.initials: RF
authors.lastname: Hariadi
authors.affiliation: Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: R F
authors.initials: RF
authors.lastname: Sommese
authors.affiliation: Department of Biochemistry, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: A S
authors.initials: AS
authors.lastname: Adhikari
authors.affiliation: Department of Biochemistry, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: R E
authors.initials: RE
authors.lastname: Taylor
authors.affiliation: Department of Biochemistry, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: S
authors.initials: S
authors.lastname: Sutton
authors.affiliation: Department of Biochemistry, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Spudich
authors.affiliation: 1] Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109, USA [2] Department of Biophysics, University of Michigan, Ann Arbor, Michigan 48109, USA [3] Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: S
authors.initials: S
authors.lastname: Sivaramakrishnan
mesh_terms: D000199:Actins / Q000737:chemistry / Q000378:metabolism; D057005:Bioengineering; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D009068:Movement / Q000502:physiology*; D009218:Myosins / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D036103:Nanotechnology; D043942:Nanotubes / Q000737:chemistry*
chemical_list: D000199:Actins; D004247:DNA; D009218:Myosins