Single myosin molecule mechanics: piconewton forces and nanometre steps
TL;DR: A new in vitro assay using a feedback enhanced laser trap system allows direct measurement of force and displacement that results from the interaction of a single myosin molecule with a single suspended actin filament.
Abstract: A new in vitro assay using a feedback enhanced laser trap system allows direct measurement of force and displacement that results from the interaction of a single myosin molecule with a single suspended actin filament. Discrete stepwise movements averaging 11 nm were seen under conditions of low load, and single force transients averaging 3-4 pN were measured under isometric conditions. The magnitudes of the single forces and displacements are consistent with predictions of the conventional swinging-crossbridge model of muscle contraction.
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TL;DR: In this article, the optimal characteristics of strength-specific programs include the use of concentric (CON), eccentric (ECC), and isometric muscle actions and the performance of bilateral and unilateral single and multiple-joint exercises.
Abstract: In order to stimulate further adaptation toward specific training goals, progressive resistance training (RT) protocols are necessary The optimal characteristics of strength-specific programs include the use of concentric (CON), eccentric (ECC), and isometric muscle actions and the performance of bilateral and unilateral single- and multiple-joint exercises In addition, it is recommended that strength programs sequence exercises to optimize the preservation of exercise intensity (large before small muscle group exercises, multiple-joint exercises before single-joint exercises, and higher-intensity before lower-intensity exercises) For novice (untrained individuals with no RT experience or who have not trained for several years) training, it is recommended that loads correspond to a repetition range of an 8-12 repetition maximum (RM) For intermediate (individuals with approximately 6 months of consistent RT experience) to advanced (individuals with years of RT experience) training, it is recommended that individuals use a wider loading range from 1 to 12 RM in a periodized fashion with eventual emphasis on heavy loading (1-6 RM) using 3- to 5-min rest periods between sets performed at a moderate contraction velocity (1-2 s CON; 1-2 s ECC) When training at a specific RM load, it is recommended that 2-10% increase in load be applied when the individual can perform the current workload for one to two repetitions over the desired number The recommendation for training frequency is 2-3 d·wk -1 for novice training, 3-4 d·wk -1 for intermediate training, and 4-5 d·wk -1 for advanced training Similar program designs are recommended for hypertrophy training with respect to exercise selection and frequency For loading, it is recommended that loads corresponding to 1-12 RM be used in periodized fashion with emphasis on the 6-12 RM zone using 1- to 2-min rest periods between sets at a moderate velocity Higher volume, multiple-set programs are recommended for maximizing hypertrophy Progression in power training entails two general loading strategies: 1) strength training and 2) use of light loads (0-60% of 1 RM for lower body exercises; 30-60% of 1 RM for upper body exercises) performed at a fast contraction velocity with 3-5 min of rest between sets for multiple sets per exercise (three to five sets) It is also recommended that emphasis be placed on multiple-joint exercises especially those involving the total body For local muscular endurance training, it is recommended that light to moderate loads (40-60% of 1 RM) be performed for high repetitions (>15) using short rest periods (<90 s) In the interpretation of this position stand as with prior ones, recommendations should be applied in context and should be contingent upon an individual's target goals, physical capacity, and training status
3,421 citations
TL;DR: Single-molecule atomic force microscopy was used to investigate the mechanical properties of titin, the giant sarcomeric protein of striated muscle, and refolding of immunoglobulin domains was observed.
Abstract: Single-molecule atomic force microscopy (AFM) was used to investigate the mechanical properties of titin, the giant sarcomeric protein of striated muscle. Individual titin molecules were repeatedly stretched, and the applied force was recorded as a function of the elongation. At large extensions, the restoring force exhibited a sawtoothlike pattern, with a periodicity that varied between 25 and 28 nanometers. Measurements of recombinant titin immunoglobulin segments of two different lengths exhibited the same pattern and allowed attribution of the discontinuities to the unfolding of individual immunoglobulin domains. The forces required to unfold individual domains ranged from 150 to 300 piconewtons and depended on the pulling speed. Upon relaxation, refolding of immunoglobulin domains was observed.
2,959 citations
TL;DR: In order to stimulate further adaptation toward a specific training goal(s), progression in the type of resistance training protocol used is necessary and emphasis should be placed on multiple-joint exercises, especially those involving the total body.
Abstract: In order to stimulate further adaptation toward a specific training goal(s), progression in the type of resistance training protocol used is necessary. The optimal characteristics of strength-specific programs include the use of both concentric and eccentric muscle actions and the performance of both single- and multiple-joint exercises. It is also recommended that the strength program sequence exercises to optimize the quality of the exercise intensity (large before small muscle group exercises, multiple-joint exercises before single-joint exercises, and higher intensity before lower intensity exercises). For initial resistances, it is recommended that loads corresponding to 8-12 repetition maximum (RM) be used in novice training. For intermediate to advanced training, it is recommended that individuals use a wider loading range, from 1-12 RM in a periodized fashion, with eventual emphasis on heavy loading (1-6 RM) using at least 3-min rest periods between sets performed at a moderate contraction velocity (1-2 s concentric, 1-2 s eccentric). When training at a specific RM load, it is recommended that 2-10% increase in load be applied when the individual can perform the current workload for one to two repetitions over the desired number. The recommendation for training frequency is 2-3 d x wk(-1) for novice and intermediate training and 4-5 d x wk(-1) for advanced training. Similar program designs are recommended for hypertrophy training with respect to exercise selection and frequency. For loading, it is recommended that loads corresponding to 1-12 RM be used in periodized fashion, with emphasis on the 6-12 RM zone using 1- to 2-min rest periods between sets at a moderate velocity. Higher volume, multiple-set programs are recommended for maximizing hypertrophy. Progression in power training entails two general loading strategies: 1) strength training, and 2) use of light loads (30-60% of 1 RM) performed at a fast contraction velocity with 2-3 min of rest between sets for multiple sets per exercise. It is also recommended that emphasis be placed on multiple-joint exercises, especially those involving the total body. For local muscular endurance training, it is recommended that light to moderate loads (40-60% of 1 RM) be performed for high repetitions (> 15) using short rest periods (< 90 s). In the interpretation of this position stand, as with prior ones, the recommendations should be viewed in context of the individual's target goals, physical capacity, and training status.
2,845 citations
Cites background from "Single myosin molecule mechanics: p..."
...Muscle fiber cross-sectional area (CSA) is positively related to maximal force production (71)....
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Journal Article•
2,160 citations
TL;DR: The construction of a DNA machine in which the DNA is used not only as a structural material, but also as ‘fuel’; each cycle produces a duplex DNA waste product.
Abstract: Molecular recognition between complementary strands of DNA allows construction on a nanometre length scale. For example, DNA tags may be used to organize the assembly of colloidal particles, and DNA templates can direct the growth of semiconductor nanocrystals and metal wires. As a structural material in its own right, DNA can be used to make ordered static arrays of tiles, linked rings and polyhedra. The construction of active devices is also possible--for example, a nanomechanical switch, whose conformation is changed by inducing a transition in the chirality of the DNA double helix. Melting of chemically modified DNA has been induced by optical absorption, and conformational changes caused by the binding of oligonucleotides or other small groups have been shown to change the enzymatic activity of ribozymes. Here we report the construction of a DNA machine in which the DNA is used not only as a structural material, but also as 'fuel'. The machine, made from three strands of DNA, has the form of a pair of tweezers. It may be closed and opened by addition of auxiliary strands of 'fuel' DNA; each cycle produces a duplex DNA waste product.
2,148 citations
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TL;DR: Recordings of the change in tension in striated muscle after a sudden alteration of the length have made it possible to suggest how the force between the thick and thin muscle filaments may be generated.
Abstract: Recordings of the change in tension in striated muscle after a sudden alteration of the length have made it possible to suggest how the force between the thick and thin muscle filaments may be generated.
2,050 citations
TL;DR: The three-dimensional structure of the head portion of myosin, or subfragment-1, which contains both the actin and nucleotide binding sites, is described, and this structure of a molecular motor was determined by single crystal x-ray diffraction.
Abstract: Directed movement is a characteristic of many living organisms and occurs as a result of the transformation of chemical energy into mechanical energy. Myosin is one of three families of molecular motors that are responsible for cellular motility. The three-dimensional structure of the head portion of myosin, or subfragment-1, which contains both the actin and nucleotide binding sites, is described. This structure of a molecular motor was determined by single crystal x-ray diffraction. The data provide a structural framework for understanding the molecular basis of motility.
1,927 citations
TL;DR: It is found that kinesin moves with 8-nm steps, similar to biological motors that move with regular steps.
Abstract: Do biological motors move with regular steps? To address this question, we constructed instrumentation with the spatial and temporal sensitivity to resolve movement on a molecular scale. We deposited silica beads carrying single molecules of the motor protein kinesin on microtubules using optical tweezers and analysed their motion under controlled loads by interferometry. We find that kinesin moves with 8-nm steps.
1,829 citations
TL;DR: There is now a real possibility of solving the problem in complete detail, provided a way can be found to crystallize a recently purified globular subfragment of the myosin molecule, and some apparently paradoxical properties of the system are revealed.
Abstract: During the last few years the basic features of the sliding-filament model of contraction in striated muscle have gained general acceptance and it has been possible to concentrate attention on the detailed mechanism by which the relative sliding force between the actin and myosin filaments is developed. A number of observations have indicated in general outline how crossbridges between the filaments may be involved in the generation of this force but have also revealed some apparently paradoxical properties of the system. The most recent findings show a possible way in which these paradoxes can be resolved. Furthermore, there is now a real possibility of solving the problem in complete detail, provided a way can be found to crystallize a recently purified globular subfragment of the myosin molecule. In this article I discuss these new findings and their implications. According to the interdigitating filament model of striated muscle (1), the contractile material consists of long series of partially overlapping arrays of actin and myosin filaments which form the myofibrils. These overlapping arrays give rise to the characteristic band pattern visible in the light microscope. In vertebrate striated muscle the myosin-containing filaments are spaced out in a hexagonal lattice 400 The Mechanism of Muscular Contraction
1,615 citations
TL;DR: The results of this study are consistent with a model in which kinesin detaches briefly from the microtubule during a part of each mechanochemical cycle, rather than a models in whichKinesin remains bound at all times.
Abstract: Kinesin, a mechanoenzyme that couples ATP hydrolysis to movement along microtubules, is thought to power vesicle transport and other forms of microtubule-based motility. Here, microscopic silica beads were precoated with carrier protein, exposed to low concentrations of kinesin, and individually manipulated with a single-beam gradient-force optical particle trap ('optical tweezers') directly onto microtubules. Optical tweezers greatly improved the efficiency of the bead assay, particularly at the lowest kinesin concentrations (corresponding to approximately 1 molecule per bead). Beads incubated with excess kinesin moved smoothly along a microtubule for many micrometres, but beads carrying from 0.17-3 kinesin molecules per bead, moved, on average, only about 1.4 microns and then spontaneously released from the microtubule. Application of the optical trap directly behind such moving beads often pulled them off the microtubule and back into the centre of the trap. This did not occur when a bead was bound by an AMP.PNP-induced rigor linkage, or when beads were propelled by several kinesin molecules. Our results are consistent with a model in which kinesin detaches briefly from the microtubule during a part of each mechanochemical cycle, rather than a model in which kinesin remains bound at all times.
1,053 citations