Design Principles and Benefits of Spatially Explicit Models of Myofilament Function.

Spatially explicit models of muscle contraction include fine-scale details about the spatial, kinetic, and/or mechanical properties of the biological processes being represented within the model network. Over the past 25 years, this has primarily consisted of a set of mathematical and computational algorithms representing myosin cross-bridge activity, Ca 2+ -activation of contraction, and ensemble force production within a half-sarcomere representation of the myofilament network. Herein we discuss basic design principles associated with creating spatially explicit models of myofilament function, as well as model assumptions underlying model development. A brief overview of computational approaches is introduced. Opportunities for new model directions that could investigate coupled regulatory pathways between the thick-filament and thin-filaments are also presented. Given the modular design and flexibility associated with spatially explicit models, we highlight some advantages of this approach compared to other model formulations.