A spatially-detailed model of actin and myosin interaction in the cardiac myofilament including strain-based rates and cooperative mechanisms

Jagir R. Hussan, Pieter P. De Tombe, John J. Rice

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

The availability of increased computing power will make new classes of biological models possible. One such class will be spatially-explicit representations of subcellular machinery. We have developed such a model of the interaction of actin and myosin within one pair of thick and thin filaments in the cardiac sarcomere. We have chosen to model the smallest repeating unit that maintains fundamental spatial interactions thought to produce important and characteristic cardiac muscle responses at cell, tissue and whole heart levels. The model discussed differs from existing models by having spatially-explicit representations of actin, myosin, regulatory protein interactions including extensible links to capture filament compliances. Sample results are compared with experimental characterizations of real muscle. The model recapitulates a wide range of complex, non-linear behavior and hence provides a plausible and quantitative explanation for several unexplained phenomena in cardiac muscle. The execution of the model demands Monte Carlo-based simulations of Markov representations of Ca regulation and actin-myosin interactions with strain-dependent rates. In addition, the solution of the compliant realignment of the thick and thin filament binding sites requires an iterative solution technique that demands substantial computational resources. The model is suitable to serve as a basis for larger scale simulations.

Original languageEnglish (US)
Title of host publicationProceedings of the Fourth IASTED International Conference on Biomedical Engineering
Pages124-132
Number of pages9
StatePublished - Dec 1 2006
Event4th IASTED International Conference on Biomedical Engineering - Innsbruck, Austria
Duration: Feb 15 2006Feb 17 2006

Publication series

NameProceedings of the Fourth IASTED International Conference on Biomedical Engineering
Volume2006

Other

Other4th IASTED International Conference on Biomedical Engineering
CountryAustria
CityInnsbruck
Period2/15/062/17/06

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Keywords

  • Actin
  • Calcium
  • Cardiac
  • Muscle
  • Myosin
  • Simulation

ASJC Scopus subject areas

  • Engineering(all)

Cite this

Hussan, J. R., De Tombe, P. P., & Rice, J. J. (2006). A spatially-detailed model of actin and myosin interaction in the cardiac myofilament including strain-based rates and cooperative mechanisms. In Proceedings of the Fourth IASTED International Conference on Biomedical Engineering (pp. 124-132). (Proceedings of the Fourth IASTED International Conference on Biomedical Engineering; Vol. 2006).