Berlin 2018 – wissenschaftliches Programm
Bereiche | Tage | Auswahl | Suche | Aktualisierungen | Downloads | Hilfe
BP: Fachverband Biologische Physik
BP 17: Cell Mechanics I
BP 17.2: Vortrag
Mittwoch, 14. März 2018, 09:45–10:00, H 1058
Substrate stiffness affects sarcomere coherence in hESC-derived cardiomyocytes — •Daniel Härtter1, Til Driehorst1,2, Malte Tiburcy2, Kengo Nishi1, Wolfram-H. Zimmermann2, and Christoph F. Schmidt1 — 1Drittes Physikalisches Institut - Biophysik, Fakultät für Physik, Georg-August-Universität Göttingen — 2Institut für Pharmakologie, Universitätsmedizin, Georg-August-Universität Göttingen
The mechanical micro-environment affects the behavior of cells. For instance, stiff infarcted heart tissue inhibits the global contraction of cardiomyocytes. However, direct insight into how the mechanical environment influences dynamics on the sarcomere level is missing. We tracked the motion of individual sarcomeres using endogeneous z-line labeling in CRISPR/Cas9 modified hESC-derived cardiomyocytes on micro-patterned substrates with various physiologically relevant stiffnesses (7 kPa to 60 kPa). Individual sarcomere contraction is impeded for increasing substrate stiffness. Furthermore, on soft substrates sarcomeres contract coherently, whereas with increasing stiffness the sarcomere contraction gets increasingly incoherent and heterogeneous.
These findings suggest that rigid mechanical surroundings force sarcomeres into competition. Using a mechanistic muscle model, we show that z-lines elastically cross-linked to the substrate and heterogeneous elements can account for many features we observe. Theories of collective molecular motors predict emerging phenomena such as dynamic instabilities, and these experiments can provide quantitative data to understand the microscopic basis of real cardiac muscle function.