Multiscale Computational Modeling of the Heart

tational models to help interpret their ex-perimental studies of the electromechani-cal properties of the normal and diseased heart, from molecular to whole-organ scales. In the models, systems of nonlinear ordinary differential and algebraic equa-tions (DAEs) describe the kinetics of bio-chemical signaling networks, the ion fluxes through voltage-gated channels, and the dynamic interactions of the contractile pro-teins responsible for cardiac muscle con-traction. Because these processes are spa-tially distributed, compartmentalized, and heterogeneous, the DAE system models must be spatially coupled and solved with numerical methods for the resulting PDEs. At the subcellular scale, the group is developing finite element models of the diffusion of calcium in the narrow (10-nm) subspace underlying the cell membrane, especially around special invaginations of the membrane into the cell interior known as transverse tubules (shown at far left in Figure 1). At the whole-cell scale (10–100 μm), spatial gradients of the signaling molecules that regulate excitation and contraction are modeled with finite volume methods and the Virtual Cell package developed by Les Loew’s National Resource for Cell Analysis and Modelin