Substrate stiffness-modulated registry phase correlations in cardiomyocytes map structural order to coherent beating

Abstract

Recent experiments show that both striation, an indication of the structural registry in muscle fibres, as well as the contractile strains produced by beating cardiac muscle cells can be optimized by substrate stiffness. Here we show theoretically how the substrate rigidity dependence of the registry data can be mapped onto that of the strain measurements. We express the elasticity-mediated structural registry as a phase-order parameter using a statistical physics approach that takes the noise and disorder inherent in biological systems into account. By assuming that structurally registered myofibrils also tend to beat in phase, we explain the observed dependence of both striation and strain measurements of cardiomyocytes on substrate stiffness in a unified manner. The agreement of our ideas with experiment suggests that the correlated beating of heart cells may be limited by the structural order of the myofibrils, which in turn is regulated by their elastic environment. Cardiomyocyte function depends on the interplay between the intracellular fibrillar organization, contraction strain and substrate stiffness. Here the authors present a model that maps the measured values of the registry striations to those of the beating strain as functions of the substrate rigidity.