Editors' ChoiceMechanotransduction

The mechanics of the first heartbeat

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Science Signaling  23 Aug 2016:
Vol. 9, Issue 442, pp. ec193
DOI: 10.1126/scisignal.aai8287

The heart is the first organ to develop and begin to function in the embryo. Chiou et al. developed a pair of mathematical models to show how these first heartbeats can occur through mechanical coupling rather than the gap junction–mediated electrical coupling that coordinates the adult heartbeat. In the models, the cardiomyocytes lacked any direct contact and were modeled as a cubic array with each cell surrounded by extracellular matrix, and mechanical strain was transmitted from cell to cell through the extracellular matrix. In the saturating eigenstrain (SE) model, the strain induced by a contracting myocyte increased to a maximum amount with the stiffness of the extracellular matrix; in the constant eigenstrain (CE) model, the strain induced by a contracting myocyte was independent of the stiffness of the extracellular matrix. Both models matched experimental data related to the velocity of the contractile wave front and the maximum tissue strain in embryonic hearts, and the SE model matched the strain on individual beating cardiomyocytes plated on gel surfaces of various stiffnesses. The models both accurately predicted the stiffness threshold of the developing heart that correlated with the switch from uncoordinated beating (a process referred to as shivering) of embryonic heart cells to coordinated beating. A key prediction of the mechanical model is that beating should be independent of the passage of ions through gap junctions. Indeed, unlike the adult hearts, embryonic chicken hearts continued beating even in the presence of high concentrations and prolonged exposure to a pharmacological inhibitor of gap junctions. Thus, similar to some of the earliest events in development, such as mesoderm invagination, mechanical signaling coordinates the beats of the developing heart.

K. K. Chiou, J. W. Rocks, C. Y. Chen, S. Cho, K. E. Merkus, A. Rajaratnam, P. Robison, M. Tewari, K. Vogel, S. F. Majkut, B. L. Prosser, D. E. Discher, A. J. Liu, Mechanical signaling coordinates the embryonic heartbeat. Proc. Natl. Acad. Sci. U.S.A 113, 8939–8944 (2016). [PubMed]

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