Dresden 2020 – wissenschaftliches Programm
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BP: Fachverband Biologische Physik
BP 38: Focus: Biological Cells in Microfluidics II
BP 38.6: Vortrag
Freitag, 20. März 2020, 11:30–11:45, HÜL 386
Bayesian parameter estimation and model selection for biophysical models of leukocyte cell extensions during leukocyte rolling — •Mats Leif Moskopp1, Philipp Rosendahl2,3, Jochen Guck2,4, Andreas Deußen1, and Peter Dieterich1 — 1Institut für Physiologie, TU Dresden, Dresden, Germany — 2Biotechnology Center, TU Dresden, Dresden, Germany — 3Zellmechanik Dresden GmbH, Dresden, Germany — 4MPL & MPZ-PM, Erlangen, Germany
The leukocyte adhesion cascade describes the extravasation of leukocytes from the blood stream into tissue. We focus on the initial process of leukocyte rolling, which is driven by shear stress and (passive) restoring forces in leukocyte cell extensions (microvilli, tethers and slings). We investigate the biomechanical properties of cell extensions based on experimental data combined with mathematical modelling and Bayesian inference. High speed (2000 fps) video sequences of rolling leukocytes (THP-1) were used to obtain cell positions as a function of time over a periode of about 10 s. Bayesian inference allows for model selection and parameter estimation of visco-elastic models (Maxwell, Kelvin-Voigt, Standard linear solid) for the fast deceleration of cell extensions during leukocyte rolling. This new technique identified differences in the biomechanical stress responses of cell extensions according to isoforms of selectins. These findings correlate to distinct rolling dynamics on P- and E-selectin isoforms regarding overall velocity and fast deceleration events. Further, this approach allows to quantify model parameters. This was tested using Glutaraldehyde (tissue fixation) and Cytochalasin D (inhibitor of actin polymerization).