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.
Tracqui
Philippe
P
Laboratoire Techniques de l'Ingéniere Médicale et da Complexité - Informatique, Mathématiques et Applications de Grenoble, Equipe DynaCell, Unité Mixte de Recherche, Centre National de Recherche Scientifique 5525, Institut d'Ingénierie et de l'Information de Santé (In3S), Université Joseph Fourier, Faculté de Médecine de Grenoble, 38706 La Tronche Cedex, France. philippe.tracqui@imag.fr
Ohayon
Jacques
J
D016880:Anisotropy; D002118:Calcium / Q000502:physiology*; D003198:Computer Simulation; D020342:Finite Element Analysis; D006801:Humans; D018715:Microscopy, Video; D008955:Models, Cardiovascular; D009200:Myocardial Contraction / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000502:physiology*; D012518:Sarcomeres / Q000502:physiology*
D002118:Calcium