A microscopically motivated model for the remodeling of cardiomyocytes
We present a thermodynamically based model that captures the remodeling effects in cardiac muscle cells. This work begins with the formulation of the kinematics of a cardiomyocyte resulting from a prescribed macroscopic deformation and the reorganization of the internal structure. Specifically, relations between the macroscopic deformation and the number of sarcomeres, the sarcomere stretch, and the number of myofibrils in the cell are determined. The remodeling process is split into two separate phases—(1) elongation/shortening of the existing myofibrils by addition/detachment of sarcomeres and (2) formation of new myofibrils. The remodeling associated with each phase is modeled through a dissipation postulate. We show that remodeling is based on a competition between the internal energy, the entropy, the energy supplied to the system by ATP and other sources to drive the remodeling process, and dissipation mechanisms. While the variations in entropy associated with phase (1) are neglected, the substantial entropy loss associated with the formation of new myofibrils is determined. To illustrate the merit of the proposed framework, we compute the response of cardiomyocytes subjected to isometric axial stretch that are either free to deform or fixed in the transverse direction. We also examine the predictions of this model for cardiomyocytes subjected to various cyclic loadings. The proposed framework is capable of capturing a wide range of remodeling effects and agrees with experimental observations.
KeywordsRemodeling in cardiomyocytes Cardiomyocytes Multi-scale modeling Statistical mechanics Actin/myosin interaction
This research was supported, in part, through an Otis Williams Postdoctoral Fellowship granted by the Santa Barbara Foundation.