24 research outputs found
A Data-Driven Computational Model for Engineered Cardiac Microtissues
Engineered heart tissues (EHTs) present a potential solution to some of the
current challenges in the treatment of heart disease; however, the development
of mature, adult-like cardiac tissues remains elusive. Mechanical stimuli have
been observed to improve whole-tissue function and cardiomyocyte (CM)
maturation, although our ability to fully utilize these mechanisms is hampered,
in part, by our incomplete understanding of the mechanobiology of EHTs. In this
work, we leverage the experimental data produced by a mechanically tunable
experimental setup to generate tissue-specific computational models of EHTs.
Using imaging and functional data, our modeling pipeline generates models with
tissue-specific ECM and myofibril structure, allowing us to estimate CM active
stress. We use this experimental and modeling pipeline to study different
mechanical environments, where we contrast the force output of the tissue with
the computed active stress of CMs. We show that the significant differences in
measured experimental forces can largely be explained by the levels of
myofibril formation achieved by the CMs in the distinct mechanical
environments, with active stress showing more muted variations across
conditions. The presented model also enables us to dissect the relative
contributions of myofibrils and extracellular matrix to tissue force output, a
task difficult to address experimentally. These results highlight the
importance of tissue-specific modeling to augment EHT experiments, providing
deeper insights into the mechanobiology driving EHT function.Comment: 19 pages, 7 figure