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

View Article: PubMed Central - PubMed

ABSTRACT

Bridging the gaps between experimental systems on different hierarchical scales is needed to overcome remaining challenges in the understanding of muscle contraction. Here, a mathematical model with well-characterized structural and biochemical actomyosin states is developed to that end. We hypothesize that this model accounts for generation of force and motion from single motor molecules to the large ensembles of muscle. In partial support of this idea, a wide range of contractile phenomena are reproduced without the need to invoke cooperative interactions or ad hoc states/transitions. However, remaining limitations exist, associated with ambiguities in available data for model definition e.g.: (1) the affinity of weakly bound cross-bridges, (2) the characteristics of the cross-bridge elasticity and (3) the exact mechanistic relationship between the force-generating transition and phosphate release in the actomyosin ATPase. Further, the simulated number of attached myosin heads in the in vitro motility assay differs several-fold from duty ratios, (fraction of strongly attached ATPase cycle times) derived in standard analysis. After addressing the mentioned issues the model should be useful in fundamental studies, for engineering of myosin motors as well as for studies of muscle disease and drug development.

Electronic supplementary material: The online version of this article (doi:10.1007/s10974-016-9458-0) contains supplementary material, which is available to authorized users.

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Sliding velocity in the in vitro motility assay vs [NEM-HMM]/[HMM] ratio where NEM-HMM is N-ethyl maleimide treated HMM. Simulated data (black) compared to experimental data (purple) from (Kim et al. 1996) (circles; fast rabbit HMM; 25 °C; ionic strength <50 mM) and (Amitani et al. 2001) (triangles, fitted with cubic polynomial; fast rabbit HMM, 25 °C; ionic strength <50 mM). Simulated behavior of long (20 µm) filaments assuming binding energy of NEM-HMM to actin of either 18 kBT (filled circles) or 7 kBT (open circles). The latter case also simulated for 1 µm long filaments (triangles). Note appreciable variability among experimental results but also variability among simulated data depending on exact conditions for the simulations. Experimental data points were obtained by measuring from figures in the cited papers
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Fig6: Sliding velocity in the in vitro motility assay vs [NEM-HMM]/[HMM] ratio where NEM-HMM is N-ethyl maleimide treated HMM. Simulated data (black) compared to experimental data (purple) from (Kim et al. 1996) (circles; fast rabbit HMM; 25 °C; ionic strength <50 mM) and (Amitani et al. 2001) (triangles, fitted with cubic polynomial; fast rabbit HMM, 25 °C; ionic strength <50 mM). Simulated behavior of long (20 µm) filaments assuming binding energy of NEM-HMM to actin of either 18 kBT (filled circles) or 7 kBT (open circles). The latter case also simulated for 1 µm long filaments (triangles). Note appreciable variability among experimental results but also variability among simulated data depending on exact conditions for the simulations. Experimental data points were obtained by measuring from figures in the cited papers

Mentions: A frictional load is often imposed on myosin propelled filaments in the in vitro motility assay (“a loaded motility assay”) (Bing et al. 2000) by transient interaction of actin binding proteins on the surface with the actin filament. Simulations, assuming NEM-HMM to be the actin-binding protein, are consistent with experiments within the quite appreciable variability (Fig. 6). Furthermore, plots of velocities against the resistive loads produced by the NEM-HMM heads compare well to force–velocity data from simulations of forces developed during iso-velocity shortening (Fig. 5).Fig. 6


Actomyosin based contraction: one mechanokinetic model from single molecules to muscle?
Sliding velocity in the in vitro motility assay vs [NEM-HMM]/[HMM] ratio where NEM-HMM is N-ethyl maleimide treated HMM. Simulated data (black) compared to experimental data (purple) from (Kim et al. 1996) (circles; fast rabbit HMM; 25 °C; ionic strength <50 mM) and (Amitani et al. 2001) (triangles, fitted with cubic polynomial; fast rabbit HMM, 25 °C; ionic strength <50 mM). Simulated behavior of long (20 µm) filaments assuming binding energy of NEM-HMM to actin of either 18 kBT (filled circles) or 7 kBT (open circles). The latter case also simulated for 1 µm long filaments (triangles). Note appreciable variability among experimental results but also variability among simulated data depending on exact conditions for the simulations. Experimental data points were obtained by measuring from figures in the cited papers
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5383694&req=5

Fig6: Sliding velocity in the in vitro motility assay vs [NEM-HMM]/[HMM] ratio where NEM-HMM is N-ethyl maleimide treated HMM. Simulated data (black) compared to experimental data (purple) from (Kim et al. 1996) (circles; fast rabbit HMM; 25 °C; ionic strength <50 mM) and (Amitani et al. 2001) (triangles, fitted with cubic polynomial; fast rabbit HMM, 25 °C; ionic strength <50 mM). Simulated behavior of long (20 µm) filaments assuming binding energy of NEM-HMM to actin of either 18 kBT (filled circles) or 7 kBT (open circles). The latter case also simulated for 1 µm long filaments (triangles). Note appreciable variability among experimental results but also variability among simulated data depending on exact conditions for the simulations. Experimental data points were obtained by measuring from figures in the cited papers
Mentions: A frictional load is often imposed on myosin propelled filaments in the in vitro motility assay (“a loaded motility assay”) (Bing et al. 2000) by transient interaction of actin binding proteins on the surface with the actin filament. Simulations, assuming NEM-HMM to be the actin-binding protein, are consistent with experiments within the quite appreciable variability (Fig. 6). Furthermore, plots of velocities against the resistive loads produced by the NEM-HMM heads compare well to force–velocity data from simulations of forces developed during iso-velocity shortening (Fig. 5).Fig. 6

View Article: PubMed Central - PubMed

ABSTRACT

Bridging the gaps between experimental systems on different hierarchical scales is needed to overcome remaining challenges in the understanding of muscle contraction. Here, a mathematical model with well-characterized structural and biochemical actomyosin states is developed to that end. We hypothesize that this model accounts for generation of force and motion from single motor molecules to the large ensembles of muscle. In partial support of this idea, a wide range of contractile phenomena are reproduced without the need to invoke cooperative interactions or ad hoc states/transitions. However, remaining limitations exist, associated with ambiguities in available data for model definition e.g.: (1) the affinity of weakly bound cross-bridges, (2) the characteristics of the cross-bridge elasticity and (3) the exact mechanistic relationship between the force-generating transition and phosphate release in the actomyosin ATPase. Further, the simulated number of attached myosin heads in the in vitro motility assay differs several-fold from duty ratios, (fraction of strongly attached ATPase cycle times) derived in standard analysis. After addressing the mentioned issues the model should be useful in fundamental studies, for engineering of myosin motors as well as for studies of muscle disease and drug development.

Electronic supplementary material: The online version of this article (doi:10.1007/s10974-016-9458-0) contains supplementary material, which is available to authorized users.

No MeSH data available.


Related in: MedlinePlus