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BP: Fachverband Biologische Physik
BP 33: Focus session: Physics of organoids
BP 33.7: Vortrag
Donnerstag, 21. März 2024, 17:00–17:15, H 1028
Multi-cellular rosette formation guides cellular rearrangement initiating lumen opening in PDAC organoids — •Marion K. Raich1, Tamara Müller1, Fridtjof Brauns3, Samuel J. Randriamanantsoa1, Ann-Caroline Heiler1, Maximilian Reichert2, and Andreas R. Bausch1 — 1Chair for Cellular Biophysics, TUM, Garching, Germany — 2Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar der TUM, Munich, Germany — 3KITP, UCSB, Santa Barbara, California 93106, USA
Organ development and tissue growth is regulated by morphogenetic programs driven by molecular motors, such as non-muscle myosin II, acting on cytoskeletal crosslinked filaments, like F-actin as well as adherens junctions proteins, e.g E-cadherin. Pancreatic ductal adenocarcinoma (PDAC) organoids, forming branched structures, were used to investigate the contribution of these protein species during distinct morphogenetic growth phases, that result in the emergence of a lumen.
Live-cell imaging of PDAC organoids showed a transformation from an elongated cell shape to an epithelial-like structure. These alterations were marked by the presence of three-dimensional rosette formations, characterized by a wedge-like geometry of the cells, with a minimum of six cells converging at a single point. Rosettes appeared periodically within the branch, having a constant distance based on its diameter. The accumulation of non-muscle myosin II and F-actin at the center of the rosette indicated that stochastically distributed actomyosin dependent force generation was required for cellular rearrangement preceding lumen formation.
Keywords: Organoids; Actomyosin force generation; Lumen formation; Pancreatic cancer; 3D rosette formation