Regensburg 2022 – wissenschaftliches Programm
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BP: Fachverband Biologische Physik
BP 3: Cell Mechanics 1
BP 3.10: Vortrag
Montag, 5. September 2022, 12:15–12:30, H15
The secret life of sarcomeres: stochastic heterogeneity of sarcomeres in beating stem-cell-derived cardiomyocytes — •Daniel Härtter1,2, Lara Hauke1, Wolfram-Hubertus Zimmermann1, and Christoph F. Schmidt2 — 1Institute of Pharmacology and Toxicology, Göttingen University Medical Center, Germany — 2Department of Physics and Soft Matter Center, Duke University, Durham, NC, USA
Sarcomeres are the basic contractile units of cardiac muscles. We tracked single sarcomere motion in individual hiPSC-derived cardiomyocytes at high resolution, using a novel set of experimental and computational tools. While the emergent cell-level motion is smooth, individual sarcomeres are highly motile and behave heterogeneously during beating cycles. In response to rigid mechanical constraints, sarcomeres are forced into a tug-of-war-like competition. Automated, machine-learning-supported analysis of a large data set (>1200 cells) indicates that sarcomere heterogeneity is not caused by static non-uniformity between sarcomeres (e.g., strong/weak), but can be primarily attributed to the stochastic and non-linear nature of sarcomere dynamics and thus occurs intrinsically during cardiomyocyte beating. We show that a simple dynamic model reproduces crucial experimental findings by assuming a non-monotonic force-velocity relation for single sarcomeres, as previously predicted for ensembles of motor proteins. This led us to a novel, active matter perspective on sarcomere motion, with sarcomeres as interacting, non-linear and stochastic agents, in contrast to the prevailing mechanistic view on muscle contraction.