Publications [#375129] of Christoph F. Schmidt
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- Daniel Haertter, Lara Hauke, Til Driehorst, Kengo Nishi, Wolfram-Hubertus Zimmermann, Christoph F. Schmidt, Tug-of-war among sarcomeres guides cardiomyocyte contraction between homogeneity and stochastic heterogeneity,
Science Advances
(Fall, 2023) .
(last updated on 2024/01/05)Abstract:
Cardiac muscle function emerges from the coordinated contraction of sarcomeres in cardiomyocytes. Sarcomere dynamics are usually inferred from whole-cell or myofibril observations, assuming a synchronized and uniform behavior. Here we investigated how varying mechanical properties of the cells’ environment affect both the cell-level and the underlying sarcomere-level contractions. Human induced pluripotent stem cell-derived cardiomyocytes with fluorescently labeled Z-bands were cultured individually on patterned elastic substrates (5 - 85 kPa). Sarcomere dynamics were precisely tracked and analyzed using SarcAsM, a machine learning algorithm we developed. Increasingly stiff substrates inhibited overall cardiomyocyte contraction, but, surprisingly, did not diminish individual sarcomere dynamics. Instead, sarcomeres competed in a tug-of-war with increasing heterogeneity and displayed rich dynamic phenomena that were not caused by static structural inhomogeneities, but occurred largely stochastically. This stochastic heterogeneity is thus an intrinsic property of cardiac sarcomere dynamics and is likely crucial for the adaptation of emergent cardiomyocyte contractility to mechanical constraints from its environment.