In collaboration with the Daniel laboratory (UW Biology), we design custom, coarse-grain simulations of myofilaments to study dynamic and kinetic properties of muscle contraction in silico. These stochastic simulations are driven by experimental observations and are used as tools to enhance our understanding of experimental data. In particular, we have recently developed spatially explicit models of a 3-dimensional, multiple myofilament half-sarcomere, which include the kinetics of thin filament activation coupled with cross-bridge cycling. These models have demonstrated the importance of sarcomere lattice geometry in cross-bridge recruitment and the Frank-Starling Law of the heart. Further development of these models will incorporate pathological conditions to investigate contractile characteristics of cardiac diseases.
- Thomas Daniel, Ph.D., Department of Biology, University of Washington
- Williams CD, Salcedo MK, Irving TC, Regnier M, Daniel TL. The length-tension curve in muscle depends on lattice spacing. Proc Biol Sci. 2013 Sep 7;280(1766):20130697. PMCID: PMC3730583.
- Williams CD, Regnier M, Daniel TL. Elastic energy storage and radial forces in the myofilament lattice depend on sarcomere length. PLoS Comput Biol. 2012;8(11):e1002770. PMCID: PMC3499250.
- Tanner BC, Daniel TL, Regnier M. Filament compliance influences cooperative activation of thin filaments and the dynamics of force production in skeletal muscle. PLoS Comput Biol. 2012;8(5):e1002506. PMCID: PMC3349719.
- Williams CD, Regnier M, Daniel TL. Axial and radial forces of cross-bridges depend on lattice spacing. PLoS Comput Biol. 2010 Dec 2;6(12):e1001018. PMCID: PMC2996315.