Hierarchical modeling of force generation in cardiac muscle Biomechanics and Modeling in Mechanobiology

Biomechanics and Modeling in Mechanobiology, 19:2567–2601 🔗📘

Abstract

Performing physiologically relevant simulations of the beating heart in clinical context requires developing detailed models of the microscale force generation process. These models however may reveal difficult to implement in practice due to their high computational costs and complex calibration. We propose a hierarchy of three interconnected muscle contraction models – from the more refined to the more simplified – that are rigorously and systematically related with each other, offering a way to select, for a specific application, the model that yields a good trade-off between physiological fidelity, computational cost and calibration complexity. The three models families are compared to the same set of experimental data to systematically assess what physiological indicators can be reproduced or not and how these indicators constrain the model parameters. Finally, we discuss the applicability of these models for heart simulation.

Main contribution

• The paper uses a novel approach for modeling the actin-myosin interaction mechanics in the context of the sliding filament paradigm. The strategy consists in representing the molecular motor dynamics as a jump-diffusion stochastic Markov process. Specifically, the conformation of the motor domain is described by a continuous Langevin process and the attachment-detachment state is captured by a binary discrete process.
• This depiction enhances the prevailing modeling framework that relies exclusively on jump processes.
• From the detailed jump-diffusion model, surrogate models are derived. These streamlined models facilitate rapid simulations, yet maintain physiological relevance, because their calibration remains consistent with the foundational refined models. The successful bridging of simple and intricate descriptions through mathematical model reduction is a pivotal contribution of this paper.

Reference

@article{kimmig-2020,
  title = {Hierarchical Modeling of Force Generation in Cardiac Muscle},
  author = {Kimmig, Fran{\c c}ois and Caruel, Matthieu},
  year = {2020},
  journal = {Biomechanics and Modeling in Mechanobiology},
  volume = {19},
  number = {6},
  pages = {2567--2601},
  doi = {10.1007/s10237-020-01357-w},
}