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

PLoS Comput Biol. 2017 Oct 2;13(10):e1005773. doi: 10.1371/journal.pcbi.1005773. eCollection 2017 Oct.

Abstract

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.

MeSH terms

  • Actins / metabolism*
  • Animals
  • Biomechanical Phenomena / physiology*
  • Computational Biology
  • Connectin / metabolism*
  • Humans
  • Models, Biological*
  • Muscle Contraction / physiology*
  • Muscle, Skeletal / physiology*

Substances

  • Actins
  • Connectin

Grants and funding

Support was provided by the European Research Council (ERC) under the European Union’s Seventh Framework Program (FP7/2007-2013) ERC grant agreement n° 306757, https://erc.europa.eu/. Moreover, the authors TH and OR would like to thank the German Research Foundation (DFG) for the financial support of the project within the Cluster of Excellence in Simulation Technology (EXC 310/1) at the University of Stuttgart, http://www.dfg.de/en/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.