An integrated formulation of anisotropic force - calcium relations driving spatio-temporal contractions of cardiac myocytes

Isolated cardiac myocytes exhibit spontaneous patterns of rhythmic contraction, driven by intracellular calcium waves. In order to study the coupling between spatio-temporal calcium dynamics and cell contraction in large deformation regimes, a new strain- energy function, describing the influence of sarcomere length on the calcium-dependent generation of active intracellular stresses, is proposed. This strain-energy function includes anisotropic passive and active contributions that were first validated separately from experimental stress-strain curves and stress-sarcomere length curves, respectively. An extended validation of this formulation was then conducted by considering this strain- energy function as the core of an integrated mechano-chemical three-dimensional model of cardiac myocyte contraction, where autocatalytic intracellular calcium dynamics were described by a representative two-variable model able to generate realistic intracellular calcium waves similar to those observed experimentally. Finite-element simulations of the three-dimensional cell model, conducted for different intracellular locations of triggering calcium sparks, explained very satisfactorily, both qualitatively and quantitatively, the contraction patterns of cardiac myocytes observed by time-lapse videomicroscopy. This integrative approach of the mechano-chemical couplings driving cardiac myocyte contraction provides a comprehensive framework for analysing active stress regulation and associated mechano-transduction processes that contribute to the efficiency of cardiac cell contractility in both physiological and pathological contexts.