4.6 Article

A continuum-mechanical skeletal muscle model including actin-titin interaction predicts stable contractions on the descending limb of the force-length relation

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PLOS COMPUTATIONAL BIOLOGY
卷 13, 期 10, 页码 -

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PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pcbi.1005773

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  1. European Research Council (ERC) under ERC [306757]
  2. German Research Foundation (DFG) within Cluster of Excellence in Simulation Technology at University of Stuttgart [EXC 310/1]
  3. European Research Council (ERC) [306757] Funding Source: European Research Council (ERC)

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Contractions on the descending limb of the total (active + passive) muscle force-length relationship (i.e. when muscle stiffness is negative) are expected to lead to vast half-sarcomere-length inhomogeneities. This is however not observed in experiments-vast half-sarcomere-length inhomogeneities can be absent in myofibrils contracting in this range, and initial inhomogeneities can even decrease. Here we show that the absence of half-sarcomere-length inhomogeneities can be predicted when considering interactions of the semi-active protein titin with the actin filaments. Including a model of actin-titin interactions within a multi-scale continuum-mechanical model, we demonstrate that stability, accurate forces and nearly homogeneous half-sarcomere lengths can be obtained on the descending limb of the static total force-length relation. This could be a key to durable functioning of the muscle because large local stretches, that might harm, for example, the transverse-tubule system, are avoided.

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