Actomyosin based contraction: one mechanokinetic model from single molecules to muscle?

Månsson, Alf

doi:10.1007/s10974-016-9458-0

Cited by 27 publications

(123 citation statements)

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“…In terms of the model in Figure 6 , each myosin head in single-molecule studies attaches to actin in the state A 1 at a given x-value. Because the attachment step is most likely rate limiting for the cycle [ 210 ], the subsequent inter-state transitions would be comparatively rapid [ 165 , 211 ] consistent with observations in ultra-fast force spectroscopy of single molecules [ 64 ]. For instance, if the free energy of the state A 2 is lower than that of state A 1 at the x-value where the cross-bridge attaches, a virtually immediate transition from state A 1 to state A 2 will follow.…”

Section: Key Cross-bridge Characteristics From Single Molecules Tomentioning

confidence: 65%

“…Other sets of classical experiments include studies of the relationship between the force developed by the muscle and the shortening or lengthening velocity (the force-velocity relationship) related to the energetics of contraction and ultrastructure [ 143 , 145 , 148 , 149 , 150 , 151 , 152 , 153 , 154 , 155 , 156 , 157 , 158 , 159 , 160 ]. Such experiments have been of critical importance for development of models for muscle contraction [ 156 , 161 , 162 , 163 , 164 , 165 , 166 , 167 , 168 , 169 ]. By being an ensemble property, the force-velocity relationship has no direct counterpart in single-molecule experiments.…”

Section: Mechanical Experiments On Muscle Cells and Myofibrils—conmentioning

confidence: 99%

“…Even more importantly, the concept is difficult to apply to an ensemble of myosin motors working together such as the myosin motors of muscle or the myosin motors in an in vitro motility assay [ 212 , 236 , 237 ]. Under these conditions, direct application of duty ratios derived using single-molecule on-times cannot predict the high sliding velocities observed [ 165 , 238 ]. The reason is that in an ensemble of motors, several of them are still propelling the actin filaments when some motors have reached the end of their power-stroke (x = 0 nm in state A 2 in Figure 6 ).…”

Section: Key Cross-bridge Characteristics From Single Molecules Tomentioning

confidence: 99%

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Do Actomyosin Single-Molecule Mechanics Data Predict Mechanics of Contracting Muscle?

Månsson

Ušaj

Moretto

et al. 2018

IJMS

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In muscle, but not in single-molecule mechanics studies, actin, myosin and accessory proteins are incorporated into a highly ordered myofilament lattice. In view of this difference we compare results from single-molecule studies and muscle mechanics and analyze to what degree data from the two types of studies agree with each other. There is reasonable correspondence in estimates of the cross-bridge power-stroke distance (7–13 nm), cross-bridge stiffness (~2 pN/nm) and average isometric force per cross-bridge (6–9 pN). Furthermore, models defined on the basis of single-molecule mechanics and solution biochemistry give good fits to experimental data from muscle. This suggests that the ordered myofilament lattice, accessory proteins and emergent effects of the sarcomere organization have only minor modulatory roles. However, such factors may be of greater importance under e.g., disease conditions. We also identify areas where single-molecule and muscle data are conflicting: (1) whether force generation is an Eyring or Kramers process with just one major power-stroke or several sub-strokes; (2) whether the myofilaments and the cross-bridges have Hookean or non-linear elasticity; (3) if individual myosin heads slip between actin sites under certain conditions, e.g., in lengthening; or (4) if the two heads of myosin cooperate.

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Section: Key Cross-bridge Characteristics From Single Molecules Tomentioning

confidence: 65%

Section: Mechanical Experiments On Muscle Cells and Myofibrils—conmentioning

confidence: 99%

Section: Key Cross-bridge Characteristics From Single Molecules Tomentioning

confidence: 99%

See 1 more Smart Citation

Do Actomyosin Single-Molecule Mechanics Data Predict Mechanics of Contracting Muscle?

Månsson

Ušaj

Moretto

et al. 2018

IJMS

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“…Major strengths of all versions of the models tested here are independent origin of model parameter values primarily from biochemical and single molecule studies of actin and myosin, as described by Månsson (2016) and Rahman et al (2018). Parameter values have further been obtained under Potma et al 1995).…”

Section: Strengths and Limitations Of The Models And Rationale Behindmentioning

confidence: 99%

The effects of inorganic phosphate on muscle force development and energetics: challenges in modelling related to experimental uncertainties

Månsson

2019

J Muscle Res Cell Motil

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Muscle force and power are developed by myosin cross-bridges, which cyclically attach to actin, undergo a force-generating transition and detach under turnover of ATP. The force-generating transition is intimately associated with release of inorganic phosphate (Pi) but the exact sequence of events in relation to the actual Pi release step is controversial. Details of this process are reflected in the relationships between [Pi] and the developed force and shortening velocity. In order to account for these relationships, models have proposed branched kinetic pathways or loose coupling between biochemical and forcegenerating transitions. A key hypothesis underlying the present study is that such complexities are not required to explain changes in the force-velocity relationship and ATP turnover rate with altered [Pi]. We therefore set out to test if models without branched kinetic paths and Pi-release occurring before the main force-generating transition can account for effects of varied [Pi] (0.1-25 mM). The models tested, one assuming either linear or non-linear cross-bridge elasticity, account well for critical aspects of muscle contraction at 0.5 mM Pi but their capacity to account for the maximum power output vary. We find that the models, within experimental uncertainties, account for the relationship between [Pi] and isometric force as well as between [Pi] and the velocity of shortening at low loads. However, in apparent contradiction with available experimental findings, the tested models produce an anomalous force-velocity relationship at elevated [Pi] and high loads with more than one possible velocity for a given load. Nevertheless, considering experimental uncertainties and effects of sarcomere nonuniformities, these discrepancies are insufficient to refute the tested models in favour of more complex alternatives.

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“…In absence of load, ⑥ is fast. Under high load as during isometric contraction, ⑥ is slow, so that g becomes similar or even lower than f. The isometric ATPase rate (ATPase ∼ 1/f + 1/g) is mainly limited by g, whereas the rate of force redevelopment (k TR ∼ f + g) is also determined by f. Models modified from (Lymn and Taylor 1971) (a) and (Dantzig et al 1992;Capitanio et al 2006;Houdusse and Sweeney 2016) Capitanio et al 2006;Siththanandan et al 2006;Caremani et al 2013;Smith 2014;Dong and Chen 2016;Geeves 2016;Houdusse and Sweeney 2016;Mansson 2016;Mijailovich et al 2017).…”

Section: Force Generation During the Cross-bridge Atpase Cycle: An Opmentioning

confidence: 99%

Kinetic coupling of phosphate release, force generation and rate-limiting steps in the cross-bridge cycle

Stehle

Tesi

2017

J Muscle Res Cell Motil

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A basic goal in muscle research is to understand how the cyclic ATPase activity of cross-bridges is converted into mechanical force. A direct approach to study the chemo-mechanical coupling between P release and the force-generating step is provided by the kinetics of force response induced by a rapid change in [P]. Classical studies on fibres using caged-P discovered that rapid increases in [P] induce fast force decays dependent on final [P] whose kinetics were interpreted to probe a fast force-generating step prior to P release. However, this hypothesis was called into question by studies on skeletal and cardiac myofibrils subjected to P jumps in both directions (increases and decreases in [P]) which revealed that rapid decreases in [P] trigger force rises with slow kinetics, similar to those of calcium-induced force development and mechanically-induced force redevelopment at the same [P]. A possible explanation for this discrepancy came from imaging of individual sarcomeres in cardiac myofibrils, showing that the fast force decay upon increase in [P] results from so-called sarcomere 'give'. The slow force rise upon decrease in [P] was found to better reflect overall sarcomeres cross-bridge kinetics and its [P] dependence, suggesting that the force generation coupled to P release cannot be separated from the rate-limiting transition. The reasons for the different conclusions achieved in fibre and myofibril studies are re-examined as the recent findings on cardiac myofibrils have fundamental consequences for the coupling between P release, rate-limiting steps and force generation. The implications from P-induced force kinetics of myofibrils are discussed in combination with historical and recent models of the cross-bridge cycle.

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Actomyosin based contraction: one mechanokinetic model from single molecules to muscle?

Cited by 27 publications

References 109 publications

Do Actomyosin Single-Molecule Mechanics Data Predict Mechanics of Contracting Muscle?

Do Actomyosin Single-Molecule Mechanics Data Predict Mechanics of Contracting Muscle?

The effects of inorganic phosphate on muscle force development and energetics: challenges in modelling related to experimental uncertainties

Kinetic coupling of phosphate release, force generation and rate-limiting steps in the cross-bridge cycle

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