Abstract
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.
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