Regensburg 2019 – scientific programme

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BP: Fachverband Biologische Physik

BP 18: Cell mechanics II

BP 18.4: Talk

Wednesday, April 3, 2019, 15:45–16:00, H10

Modeling of T-Cell polarization — •Ivan Hornak and Heiko Rieger — Saarland University, Center for Biophysics, Theoretical Physics Saarbrücken, Germany

Cytotoxic T lymphocytes (T) and natural killer (NK) cells are the main cytotoxic killer cells of the human body to eliminate pathogen-infected or tumorigenic cells (i.e. target cells). They form a tight contact, the immunological synapse (IS), with targets and release their lytic granules containing perforin/granzyme and cytokine containing vesicles. Once a NK or T cell has identified a target cell and established a contact zone one observes a re-polarization of the cell involving the rotation of the microtubule (MT) half-spindle and a movement of the centrosome or microtubule organizing center (MTOC) to a position that is just underneath the plasma membrane at the center of the IS. Concomitantly a massive relocation of organelles attached to MTs is observed, including the Golgi apparatus, lytic granules and mitochondria. Since the mechanism of this relocation is poorly understood we devised a theoretical model for the molecular motor driven motion of the MT half-spindle confined between plasma membrane and nucleus during T cell polarization. We analyze different scenarios currently discussed in the literature, including cortical sliding and capture shrinkage mechanism, and compare quantitative predictions about the spatio-temporal evolution of MTOC position and spindle morphology with experimental observations. We propose that our model opens a way to infer details of the molecular motor distribution from the experimentally observed features of the MT half-spindle dynamics.