Skeletal muscle resists stretch by rapid binding of the second motor domain of myosin to actin

Brunello, Elisabetta; Reconditi, Massimo; Elangovan, Ravikrishnan; Linari, Marco; Sun, Yin-Biao; Narayanan, Theyencheri; Panine, Pierre; Piazzesi, Gabriella; Irving, Malcolm; Lombardi, Vincenzo

doi:10.1073/pnas.0707626104

Cited by 102 publications

(111 citation statements)

References 35 publications

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“…A previous structural model for the thick filament during maximal activation (10) was modified by adding a "resting" (R) population of myosin heads to the "attached" (A) and "detached" (D) populations considered before, as described earlier. Essentially the same results were obtained with a more complicated structural model in which the two heads of each myosin molecule were treated explicitly (29), and with a model in which the light-chain domains of the A heads had a Gaussian rather than a uniform angular distribution. The A, D, and R populations have the same axial periodicity and diffract coherently.…”

Section: Methodssupporting

confidence: 52%

Motion of myosin head domains during activation and force development in skeletal muscle

Reconditi

Brunello²,

Linari³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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114

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Muscle contraction is driven by a change in the structure of the head domain of myosin, the "working stroke" that pulls the actin filaments toward the midpoint of the myosin filaments. This movement of the myosin heads can be measured very precisely in intact muscle cells by X-ray interference, but until now this technique has not been applied to physiological activation and force generation following electrical stimulation of muscle cells. By using this approach, we show that the long axes of the myosin head domains are roughly parallel to the filaments in resting muscle, with their center of mass offset by approximately 7 nm from the C terminus of the head domain. The observed mass distribution matches that seen in electron micrographs of isolated myosin filaments in which the heads are folded back toward the filament midpoint. Following electrical stimulation, the heads move by approximately 10 nm away from the filament midpoint, in the opposite direction to the working stroke. The time course of this motion matches that of force generation, but is slower than the other structural changes in the myosin filaments on activation, including the loss of helical and axial order of the myosin heads and the change in periodicity of the filament backbone. The rate of force development is limited by that of attachment of myosin heads to actin in a conformation that is the same as that during steadystate isometric contraction; force generation in the actin-attached head is fast compared with the attachment step.C ontraction of skeletal muscles is driven by a cyclical interaction between myosin and actin, fueled by the hydrolysis of ATP. The myosin and actin are polymerized into parallel thick and thin filaments, which themselves are organized into a hexagonal array in the muscle cell. The head domains of myosin lie on the surface of the thick filaments and bind to actin in the thin filaments. Filament sliding is driven by a change in conformation of the actin-bound myosin head: its working stroke (1-3). A detailed molecular model for the working stroke has been derived from biochemical and structural studies of isolated myosin head domains and their interaction with actin and ATP (3-6), and the quasi-crystalline organization of myosin and actin in muscle has allowed this model to be tested and elaborated by mechanical and structural studies on muscle cells (1, 2, 7-11).Many of these cell-based studies used rapid perturbations to synchronize the actions of the myosin heads in a muscle cell. Typically, the length of an active muscle fiber was rapidly decreased, displacing each set of myosin filaments by a few nanometers with respect to the opposing actin filaments (2). Such a shortening step produces an elastic force decrease during the step, followed in the next few milliseconds by rapid force regeneration driven by the working stroke in actin-attached myosin heads (2,7,8). This and related protocols have revealed fundamental properties of the working stroke, including its size, speed, and load dependence, and shown how ...

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Section: Methodssupporting

confidence: 52%

Motion of myosin head domains during activation and force development in skeletal muscle

Reconditi

Brunello²,

Linari³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

114

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“…This effect of stretch is not caused by the sarcomere length itself or force: the rate of P i release during stretch remains constant for the 300-ms duration of the stretch, although sarcomere length and force vary during this time. Stretch simultaneously detaches actin-attached cross-bridges that have extended beyond their attachment range and causes detached crossbridges to rapidly attach to the thin filaments, as determined by a stretch-induced increase in stiffness (24,25). Within the time resolution of our experiment, the change in rate of P i release occurs simultaneously with the application of the stretch: a direct effect of strain on the cross-bridge ATPase site.…”

Section: Discussionmentioning

confidence: 72%

“…Cross-bridge Attachment and the Rate of P i Release-Stretch causes rapid attachment of detached cross-bridges, as shown by low angle x-ray diffraction and stiffness measurements (24,25). We show here that cross-bridge attachment is paradoxically accompanied by a slower P i release compared with that in the isometric state: stretch-induced strain reduces P i release from attached cross-bridges.…”

Section: Discussionmentioning

confidence: 76%

Stretch of Contracting Cardiac Muscle Abruptly Decreases the Rate of Phosphate Release at High and Low Calcium

Mansfield

West

Curtin

et al. 2012

Journal of Biological Chemistry

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Background: Phosphate is released by the cardiac actomyosin ATPase during contraction. Results: Stretching active cardiac muscle decreases phosphate release within milliseconds. Conclusion: Mechanical stimuli such as stretch cause an immediate change in actomyosin ATPase kinetics. Significance: Stretch facilitates a powerful contraction by increasing cross-bridges in a pre-power stroke state, and changes cytoplasmic phosphate flux, which may influence energetic homeostasis.

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“…S5E) when f A is 0.18 (the associated error is in Table 1) and the LCD tilt is 63°to the filament axis, so that the displacement of the center of the mass density profile from the head-rod junction is +3.03 nm (Fig. S5B, red), 1 nm away from the center of the sarcomere with respect to the partner motors (25,27).…”

Section: Sl-tension Relationmentioning

confidence: 99%

Myosin filament activation in the heart is tuned to the mechanical task

Reconditi

Caremani

Pinzauti

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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The mammalian heart pumps blood through the vessels, maintaining the dynamic equilibrium in a circulatory system driven by two pumps in series. This vital function is based on the fine-tuning of cardiac performance by the Frank-Starling mechanism that relates the pressure exerted by the contracting ventricle (end systolic pressure) to its volume (end systolic volume). At the level of the sarcomere, the structural unit of the cardiac myocytes, the Frank-Starling mechanism consists of the increase in active force with the increase of sarcomere length (length-dependent activation). We combine sarcomere mechanics and micrometer-nanometer-scale X-ray diffraction from synchrotron light in intact ventricular trabeculae from the rat to measure the axial movement of the myosin motors during the diastole-systole cycle under sarcomere length control. We find that the number of myosin motors leaving the off, ATP hydrolysis-unavailable state characteristic of the diastole is adjusted to the sarcomere length-dependent systolic force. This mechanosensing-based regulation of the thick filament makes the energetic cost of the systole rapidly tuned to the mechanical task, revealing a prime aspect of the Frank-Starling mechanism. The regulation is putatively impaired by cardiomyopathycausing mutations that affect the intramolecular and intermolecular interactions controlling the off state of the motors. myosin filament mechanosensing | heart regulation | small-angle X-ray diffraction | cardiac muscle | Frank-Starling mechanism I n each sarcomere, the structural unit of the skeletal and cardiac muscles, myosin motors arranged in antiparallel arrays in the two halves of the thick myosin-containing filament work cooperatively, generating force and shortening by cyclic ATPdriven interactions with the interdigitating thin actin-containing filaments. The textbook model for the activation of contraction indicates that the binding to actin of myosin motors from the neighboring thick filament is controlled by a calcium-dependent structural change in the thin filament. However, in these muscles at rest, most of the myosin motors are in the off state and packed into helical tracks with 43-nm periodicity on the surface of the thick filaments (1-4), making them unavailable for binding to the thin filament and ATP hydrolysis (5, 6). Recent X-ray diffraction experiments on single fibers from skeletal muscle showed that, in addition to the canonical thin filament activation system, a thick filament mechanosensing mechanism provides a way for selective unlocking of myosin motors during high load contraction (7). This thick filament-based regulation has not yet been shown in cardiac muscle, in which several regulatory systems are significant. In contrast to skeletal muscle, during heart contraction, the internal concentration of Ca 2+ ([Ca 2+ ] i ) may not reach the full activation level, and thus, the mechanical response depends on both [Ca 2+ ] i and the sensitivity of the filaments to Ca 2+ (8, 9). For a given [Ca 2+ ] i , the maximal force i...

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Skeletal muscle resists stretch by rapid binding of the second motor domain of myosin to actin

Cited by 102 publications

References 35 publications

Motion of myosin head domains during activation and force development in skeletal muscle

Motion of myosin head domains during activation and force development in skeletal muscle

Stretch of Contracting Cardiac Muscle Abruptly Decreases the Rate of Phosphate Release at High and Low Calcium

Myosin filament activation in the heart is tuned to the mechanical task

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