Biophysical Society Thematic Meeting | Canterbury 2023

Towards a More Perfect Union: Multi-Scale Models of Muscle and Their Experimental Validation

Monday Speaker Abstracts

A CONSTRAINED MIXTURE MODEL OF SARCOMERE TURNOVER IN CARDIOMYOCYTES FOR ORGAN-SCALE CARDIAC GROWTH AND REMODELING Amadeus M Gebauer 1 ; Martin R Pfaller 2,3,4 ; Wolfgang A Wall 1 ; 1 Technical University of Munich, Institute of Computational Mechanics, Munich, Germany 2 Stanford University, Pediatric Cardiology, Stanford, CA, USA 3 Stanford University, Stanford Maternal & Child Health Research Institute, Stanford, CA, USA 4 Stanford University, Institute for Computational and Mathematical Engineering, Stanford, CA, USA Changes in the mechanical environment in the heart wall (e.g., caused by cardiovascular diseases) trigger cardiac growth and remodeling (G&R), eventually leading to heart failure in many patients. An important mechanism of G&R in soft tissue is turnover, which is the continual deposition and degradation of tissue constituents. We propose a novel model of sarcomere turnover in cardiomyocytes based on the constrained mixture model and a rheological model of sarcomeres. The rheological model of the sarcomeres includes passive and active contributions. Sarcomeres continuously replace themselves or even grow or shrink in number when cardiomyocytes are perturbed from their preferred mechanical environment. Existing models often do not explicitly model the effect of turnover on the active part of the tissue. We combine our novel sarcomere turnover model with the existing G&R model of the extracellular matrix in our finite-element-based simulation framework. We apply our model to a patient specific bi-ventricular heart and show how changes in the mechanical environment of cardiomyocytes induced by different overload conditions result in organ-scale G&R. We identify mechanobiological stable and unstable growth depending on the severity of hypertension and different growth factors. Furthermore, we elaborate on how our model predicts the reversal of G&R after returning blood pressure to baseline. Our microstructure-motivated model of organ scale cardiac G&R, together with experimental data from biomimetic cultures of living human myocardium and clinical data of long-term cardiac magnetic resonance imaging of patients has the potential to not only increase understanding but also identify patients at risk of heart failure and assess or even improve their personalized therapy options.

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