The University of Tokyo Department of Mechanical Engineering,Fracture Mechanics Laboratory.SAKAI & IZUMI group.

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A Cardiomyocyte model integrating Electrophysiology and Mechanics

Contraction of every cardiomyocyte realizes heartbeat, which is vital for our lives. Morphological disruption of subcellular structures has been reported in heart diseases, although the complex nature of the cardiac electrophysiology–contraction coupling process makes it difficult to experimentally establish causal relationships between subcellular disruption and cardiac dysfunction. We developed electrophysiology-mechanics-coupling finite element model of cardiomyocyte in which subcellular structures are modeled and realistically arranged. This model reproduced the Ca2+ transients and contraction observed in experimental studies [1]. We investigated asynchronous contraction caused by deletion of t-tubules [2], the importance of juxtaposition of mitochondria and Ca2+ release site on cardiac energy balance [3], and distinct functional roles of mitochondrial subpopulations [4]. Our integrated model of cardiomyocyte provides a powerful tool for the study of cardiac function by expanding the temporal and spatial resolution beyond the limit in experimental approaches.

 

References

[1] Hatano et al. A 3-D simulation model of cardiomyocyte integrating excitation-contraction coupling and metabolism. Biophysical Journal, 101(11):2601-2610, 2011

[2] Hatano et al. Critical role of cardiac t-tubule system for the maintenance of contractile function revealed by a 3D integrated model of cardiomyocytes. Journal of Biomechanics, 45(5):815-823, 2012 [3] Hatano et al. Mitochondrial Colocalization with Ca2+ Release Sites is Crucial to Cardiac Metabolism. Biophysical Journal, 104(2):496-504, 2013

[4] Hatano et al. Distinct Functional Roles of Cardiac Mitochondrial Subpopulations Revealed by a 3D Simulation Model. Biophysical Journal, 108(11):2732–2739, 2015


cardiomyocyte

3D presentation of finite element model and schematics of a cardiomyocyte



 








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