Proposing a Caputo-Land System for active tension. Capturing variable viscoelasticity

Abstract

Accurate cell-level active tension modeling for cardiomyocytes is critical to understanding cardiac functionality on a subject-specific basis. However, cell-level models in the literature fail to account for viscoelasticity and inter-subject variations in active tension, which are relevant to disease diagnostics and drug screening, e.g., for cardiotoxicity. Thus, we propose a fractional order system to model cell-level active tension by extending Land's state-of-the-art model of cardiac contraction. Our approach features the (left) Caputo derivative of six state variables that identify the mechanistic origins of viscoelasticity in a myocardial cell in terms of the thin filament, thick filament, and length-dependent interactions. This proposed CLS is the first of its kind for active tension modeling in cells and demonstrates notable subject-specificity, with smaller mean square errors than the reference model relative to cell-level experiments across subjects, promising greater clinical relevance than its counterparts in the literature by highlighting the contribution of different cellular mechanisms to apparent viscoelastic cell behavior, and how it could vary with disease.