VeranstaltungThe secret life of sarcomeres: deep phenotyping of the intracellular structure and function of cardiac muscle cells
|Titel der Veranstaltung||The secret life of sarcomeres: deep phenotyping of the intracellular structure and function of cardiac muscle cells|
|Reihe||CIDAS lecture series|
|Veranstalter||Campus-Institut Data Science (CIDAS)|
|Referent/in||Dr. Daniel Härtter|
|Einrichtung Referent/in||Institute of Pharmacology and Toxicology, UMG Göttingen|
|Beschreibung||Sarcomeres are the basic functional units of the heart, converting chemical energy ATP to
contractile motion. Inside cardiac muscle cells (cardiomyocytes), large numbers of
sarcomeres ordered in parallel and in series enable a strong and rapid cell-level contraction.
While sarcomeres are well understood on the molecular level, little is known about the
mesoscopic length-scale of sarcomeres: how do sarcomeres self-organize over long timeperiods and how does cellular contraction emerge from the stochastic dynamics of single
We pursue a data-driven approach to study structure and dynamics of sarcomeres in stemcell derived cardiomyocytes. With an endogenous fluorescent sarcomere reporter (ACTN2-
citrine using CRISPR/Cas9) and high-throughput confocal microscopy, we are able to (1)
continuously observe the self-organization of sarcomeres over 2 weeks and (2) track the
dynamics of individual sarcomeres at high temporal and spatial resolution on the millisecond
time-scale. The recorded microscopy movies are analyzed with a custom fully automatized
deep-learning based algorithm (SarcAsM - Sarcomere Analysis Multitool), which robustly
extracts various structural features of sarcomere organization and precisely tracks singlesarcomere motion. This high-throughput pipeline allows us to phenotypically study the
chronic and acute effect of drugs and diseases.
Single sarcomere tracking revealed highly stochastic and heterogeneous motion of single
sarcomeres. While the emergent cell-level motion is very smooth, rigid mechanical
constraints force sarcomeres into a tug-of-war like competition driving dynamic
heterogeneity. Analysis of a large data set (>1200 cells) indicates that sarcomere
heterogeneity is not caused by static non-uniformity among sarcomeres (e.g., strong/weak
units), 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 non-monotonic forcevelocity relations 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.
|Zeit||Beginn: 15.12.2022, 14:15 Uhr
Ende: 15.12.2022 , 15:15 Uhr
Anderer Ort / Other Location
Informatik Provisorium Raum 0.102. Das Informatik Provisorium ist nahe der Goldschmidtstraße 1 zu finden.