Biophysical Society Thematic Meeting | Canterbury 2023

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

Poster Abstracts

25-POS Board 25 DO TEMPERATURE AND STIMULATION FREQUENCY MATTER WHEN RECORDING CARDIAC TWITCHES? Momcilo Prodanovic 1,2,3 ; Andjela Grujic 3,4 ; Corrado Poggesi 5 ; Michael Regnier 6 ; Thomas C Irving 7 ; Michael A Geeves 8 ; Srboljub M Mijailovich 3 ; 1 University of Kragujevac, Faculty of Engineering, Kragujevac, Serbia 2 Institute for Information Technologies, University of Kragujevac, Department of technical and technological sciences, Kragujevac, Serbia 3 FilamenTech, Inc., Newton, MA, USA 4 University of Belgrade, Faculty of Physics, Belgrade, Serbia 5 University of Florence, Department of Experimental & Clinical Medicine, Florence, Italy 6 University of Washington, Department of Bioengineering, Seattle, WA, USA 7 Illinois Institute of Technology, Department of Biology, Chicago, IL, USA 8 University of Kent, Department of Biosciences, Canterbury, United Kingdom Functional changes of cardiac muscle, triggered by mutations in sarcomere proteins, are typically assessed in experiments with trabeculae from transgenic rodent models while experiments on human cardiac tissue are scarce. Mechanical responses to intracellular calcium in trabeculae are usually assessed as transient twitch contractions. Studies of twitch contractions in either rodent or human cardiac muscle, however, are often done at temperatures and frequencies that significantly differ from physiological which can make interpretation problematic. Extrapolating results from rodents to humans can also be difficult due to the differences in physiological ranges of frequ encies and myosin α and β isoform content. We are developing a novel methodology to translate findings from rodents to humans using the MUSICO computational simulation platform. The MUSICO platform embodies detailed schemes for crossbridge cycling, thin and thick filament regulation by calcium, an explicit sarcomere 3D geometry allowing for spatially randomly distributed mixture of myosin isoforms and structural features specifically adjusted for each species. As such, it is well suited as a tool to translate findings between species. Using these simulations, tightly coupled with the experiments, we quantitatively estimated the effects of temperature and stimulation frequency on tension transients in rat trabeculae. We compared model predictions with a consistent set of data from twitches in rat trabeculae which contained simultaneously recorded calcium transients and tension responses. The crossbridge cycle parameters were adjusted for temperature and used for simulations at different frequencies. The predicted twitch responses, matched with the experimental observations, served as a matrix for translation of parameters and calcium transients between species, as for example, simulating functional changes in human ventricular trabeculae when the muscle is stimulated at different frequencies and temperatures. This methodology can be extended to predict functional changes in human cardiac muscle with disease.

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