Mechanical properties of single myosin molecules probed with the photonic force microscope.

To characterize elastic properties and geometrical parameters of individual, whole myosin molecules during their interaction with actin we sparsely adsorbed myosin molecules to nanometer-sized microspheres. Thermally driven position fluctuations of these microspheres were recorded with the three-dimensional detection scheme of the photonic force microscope. Upon binding of single myosin molecules to immobilized actin filaments in the absence of ATP, these thermally driven position fluctuations of the microspheres change significantly. From three-dimensional position fluctuations stiffness and geometrical information of the tethering molecule can be derived. Axial stiffness was found to be asymmetric, approximately 0.04 pN/nm for extension, approximately 0.004 pN/nm for compression. Observed stiffness of whole myosin molecules is much less than estimated for individual myosin heads in muscle fibers or for single-molecule studies on myosin fragments. The stiffness reported here, however, is identical to stiffness found in other single-molecule studies with full-length myosin suggesting that the source of this low stiffness is located outside the myosin head domain. Analysis of geometrical properties of tethering myosin molecules by Brownian dynamics computer simulations suggests a linker length of approximately 130 nm that is divided by a free hinge located approximately 90 nm above the substrate. This pivot location coincides with myosin's hinge region. We demonstrate the general applicability of thermal fluctuation analysis to determine elastic properties and geometrical factors of individual molecules.

[1]  A. Huxley Muscular contraction. Review lecture , 1974 .

[2]  Kazuhiko Kinosita,et al.  Unbinding force of a single motor molecule of muscle measured using optical tweezers , 1995, Nature.

[3]  J. Spudich,et al.  Myosin movement in vitro: a quantitative assay using oriented actin cables from Nitella. , 1986, Methods in enzymology.

[4]  S. Ishiwata,et al.  Characterization of single actomyosin rigor bonds: load dependence of lifetime and mechanical properties. , 2000, Biophysical journal.

[5]  G. Piazzesi,et al.  Elastic bending and active tilting of myosin heads during muscle contraction , 1998, Nature.

[6]  M. Walker,et al.  Negative staining of myosin molecules. , 1985, Journal of molecular biology.

[7]  S. Tideswell,et al.  Filament compliance and tension transients in muscle , 1996, Journal of Muscle Research & Cell Motility.

[8]  G. Piazzesi,et al.  Conformation of the myosin motor during force generation in skeletal muscle. , 2000 .

[9]  L. Goldstein,et al.  Bead movement by single kinesin molecules studied with optical tweezers , 1990, Nature.

[10]  B. Brenner,et al.  Mutation of the myosin converter domain alters cross-bridge elasticity , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[11]  B. Brenner,et al.  Actin sliding on reconstituted myosin filaments containing only one myosin heavy chain isoform , 2004, Journal of Muscle Research & Cell Motility.

[12]  E. Stelzer,et al.  Photonic force microscope based on optical tweezers and two-photon excitation for biological applications. , 1997, Journal of structural biology.

[13]  H E Huxley,et al.  The Mechanism of Muscular Contraction , 1965, Scientific American.

[14]  J. Spudich,et al.  Single myosin molecule mechanics: piconewton forces and nanometre steps , 1994, Nature.

[15]  A. Huxley Muscle structure and theories of contraction. , 1957, Progress in biophysics and biophysical chemistry.

[16]  Toshio Yanagida,et al.  Sliding movement of single actin filaments on one-headed myosin filaments , 1987, Nature.

[17]  Y Ueno,et al.  X-ray diffraction evidence for the extensibility of actin and myosin filaments during muscle contraction. , 1994, Biophysical journal.

[18]  H E Huxley,et al.  X-ray diffraction measurements of the extensibility of actin and myosin filaments in contracting muscle. , 1994, Biophysical journal.

[19]  J. D. Pardee,et al.  [18] Purification of muscle actin , 1982 .

[20]  J. Spudich,et al.  Assays for actin sliding movement over myosin-coated surfaces. , 1991, Methods in enzymology.

[21]  B. Brenner,et al.  Equilibration and exchange of fluorescently labeled molecules in skinned skeletal muscle fibers visualized by confocal microscopy. , 1995, Biophysical journal.

[22]  B. Brenner,et al.  Structures of actomyosin crossbridges in relaxed and rigor muscle fibers. , 1989, Biophysical journal.

[23]  M. Rodgers,et al.  Hinging of rabbit myosin rod. , 1987, Biochemistry.

[24]  J. Happel,et al.  Low Reynolds number hydrodynamics , 1965 .

[25]  S. Highsmith,et al.  Flexibility of myosin rod, light meromyosin, and myosin subfragment-2 in solution. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[26]  B. Brenner,et al.  Parallel inhibition of active force and relaxed fiber stiffness by caldesmon fragments at physiological ionic strength and temperature conditions: additional evidence that weak cross-bridge binding to actin is an essential intermediate for force generation. , 1995, Biophysical journal.

[27]  Toshio Yanagida,et al.  A single myosin head moves along an actin filament with regular steps of 5.3 nanometres , 1999, Nature.

[28]  J. Spudich,et al.  The neck region of the myosin motor domain acts as a lever arm to generate movement. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[29]  G. Offer,et al.  Shape and flexibility of the myosin molecule. , 1978, Journal of molecular biology.

[30]  T. Yanagida,et al.  Orientation dependence of displacements by a single one-headed myosin relative to the actin filament. , 1998, Biophysical journal.

[31]  R. T. Tregear,et al.  Movement and force produced by a single myosin head , 1995, Nature.

[32]  T. Yanagida,et al.  Direct measurement of stiffness of single actin filaments with and without tropomyosin by in vitro nanomanipulation. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[33]  B. Brenner,et al.  A single-fiber in vitro motility assay. In vitro sliding velocity of F-actin vs. unloaded shortening velocity in skinned muscle fibers , 1999, Journal of Muscle Research & Cell Motility.

[34]  T. Yanagida,et al.  Compliance of thin filaments in skinned fibers of rabbit skeletal muscle. , 1995, Biophysical journal.

[35]  T. Yanagida,et al.  Multiple- and single-molecule analysis of the actomyosin motor by nanometer-piconewton manipulation with a microneedle: unitary steps and forces. , 1996, Biophysical journal.

[36]  M. Bartoo,et al.  The stiffness of rabbit skeletal actomyosin cross-bridges determined with an optical tweezers transducer. , 1998, Biophysical journal.

[37]  A. Huxley,et al.  Proposed Mechanism of Force Generation in Striated Muscle , 1971, Nature.

[38]  A. Mehta,et al.  Detection of single-molecule interactions using correlated thermal diffusion. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[39]  K. Takahashi,et al.  Topography of the myosin molecule as visualized by an improved negative staining method. , 1978, Journal of biochemistry.

[40]  Hiroto Tanaka,et al.  Simultaneous Observation of Individual ATPase and Mechanical Events by a Single Myosin Molecule during Interaction with Actin , 1998, Cell.

[41]  T. Kobayashi,et al.  Contraction characteristics and ATPase activity of skeletal muscle fibers in the presence of antibody to myosin subfragment 2. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[42]  A. Huxley,et al.  The relation between stiffness and filament overlap in stimulated frog muscle fibres. , 1981, The Journal of physiology.

[43]  E. Stelzer,et al.  Photonic force microscope calibration by thermal noise analysis , 1998 .

[44]  E. Stelzer,et al.  Three‐dimensional high‐resolution particle tracking for optical tweezers by forward scattered light , 1999, Microscopy research and technique.

[45]  T. Ando,et al.  Innocuous labeling of the subfragment-2 region of skeletal muscle heavy meromyosin with a fluorescent polyacrylamide nanobead and visualization of individual heavy meromyosin molecules. , 1996, Journal of biochemistry.