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A mathematical model of muscle containing heterogeneous half-sarcomeres exhibits residual force enhancement.

ABSTRACT: A skeletal muscle fiber that is stimulated to contract and then stretched from L? to L? produces more force after the initial transient decays than if it is stimulated at L?. This behavior has been well studied experimentally, and is known as residual force enhancement. The underlying mechanism remains controversial. We hypothesized that residual force enhancement could reflect mechanical interactions between heterogeneous half-sarcomeres. To test this hypothesis, we subjected a computational model of interacting heterogeneous half-sarcomeres to the same activation and stretch protocols that produce residual force enhancement in real preparations. Following a transient period of elevated force associated with active stretching, the model predicted a slowly decaying force enhancement lasting >30 seconds after stretch. Enhancement was on the order of 13% above isometric tension at the post-stretch muscle length, which agrees well with experimental measurements. Force enhancement in the model was proportional to stretch magnitude but did not depend strongly on the velocity of stretch, also in agreement with experiments. Even small variability in the strength of half-sarcomeres (2.1% standard deviation, normally distributed) was sufficient to produce a 5% force enhancement over isometric tension. Analysis of the model suggests that heterogeneity in half-sarcomeres leads to residual force enhancement by storing strain energy introduced during active stretch in distributions of bound cross-bridges. Complex interactions between the heterogeneous half-sarcomeres then dissipate this stored energy at a rate much slower than isolated cross-bridges would cycle. Given the variations in half-sarcomere length that have been observed in real muscle preparations and the stochastic variability inherent in all biological systems, half-sarcomere heterogeneity cannot be excluded as a contributing source of residual force enhancement.

SUBMITTER: Campbell SG

PROVIDER: S-EPMC3182863 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

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A mathematical model of muscle containing heterogeneous half-sarcomeres exhibits residual force enhancement.

Campbell Stuart G SG Hatfield P Chris PC Campbell Kenneth S KS

PLoS computational biology 20110929 9

A skeletal muscle fiber that is stimulated to contract and then stretched from L₁ to L₂ produces more force after the initial transient decays than if it is stimulated at L₂. This behavior has been well studied experimentally, and is known as residual force enhancement. The underlying mechanism remains controversial. We hypothesized that residual force enhancement could reflect mechanical interactions between heterogeneous half-sarcomeres. To test this hypothesis, we subjected a computational mo ...[more]

PMID: 21980268

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Project description:The sarcomere length non-uniformity theory (SLNT) is a widely accepted explanation for residual force enhancement (RFE). RFE is the increase in steady-state isometric force following active muscle stretching. The SLNT predicts that active stretching of a muscle causes sarcomere lengths (SL) to become non-uniform, with some sarcomeres stretched beyond actin-myosin filament overlap (popping), causing RFE. Despite being widely known, this theory has never been directly tested. We performed experiments on isolated rabbit muscle myofibrils (n?=?12) comparing SL non-uniformities for purely isometric reference contractions (I-state) and contractions following active stretch producing RFE (FE-state). Myofibrils were activated isometrically along the descending limb of the force-length relationship (mean?±?1 standard deviation (SD)?=?2.8?±?0.3?µm sarcomere(-1)). Once the I-state was reached, myofibrils were shortened to an SL on the plateau of the force-length relationship (2.4?µm sarcomere(-1)), and then were actively stretched to the reference length (2.9?±?0.3?µm sarcomere(-1)). We observed RFE in all myofibrils (39?±?15%), and saw varying amounts of non-uniformity (1 SD?=?0.9?±?0.5?µm) that was not significantly correlated with the amount of RFE, but through pairwise comparisons was found to be significantly greater than the non-uniformity measured for the I-state (0.7?±?0.4?µm). Three myofibrils exhibited no increase in non-uniformity. Active stretching was accompanied by sarcomere popping in four myofibrils, and seven had popped sarcomeres in the I-state. These results suggest that, while non-uniformities are present with RFE, they are also present in the I-state. Furthermore, non-uniformity is not associated with the magnitude of RFE, and myofibrils that had no increase in non-uniformity with stretch still showed normal RFE. Therefore, it appears that SL non-uniformity is a normal associate of muscle contraction, but does not contribute to RFE following active stretching of isolated skeletal muscle myofibrils.

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A mathematical model of muscle containing heterogeneous half-sarcomeres exhibits residual force enhancement.

Publications

A mathematical model of muscle containing heterogeneous half-sarcomeres exhibits residual force enhancement.

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