Mapping amoeboid cell migration
Till Bretschneider , Warwick Systems Biology Centre, University of Warwick, UK .
Extracellular gradients of chemoattractants or mechanical signals can guide cell movement by directing polymerization of actin, the cellular motor, to the leading edge.
Various mathematical models have been proposed which describe gradient sensing and cell polarization, mostly in terms of local excitation and global inhibition mechanisms related to original work on biological pattern formation by Turing.
I will present approaches how imaging data can be used to put these models to the test. We parameterize competing reaction-diffusion models employing experimental data of actin redistributions in Dictyostelium cells, which reorient to alternating gradients of shear flow. I will address in particular problems of parameter identifiability, related to whether a given mathematical model possesses a unique solution.
In another mode of cell motility, namely blebbing, hydrostatic pressure forces the cell membrane to detach from the underlying actin cortex, creating protrusions in form of hemispherical blebs. Dictyostelium cells sandwiched between a coverslip and a sheet of agar chemotax by employing a mixed mode of actin protrusions and blebs.
A detailed analysis of cell shape dynamics allowed us to study how blebs and actin driven protrusions interact. Results suggest that changes in geometry incurred by actin driven protrusions could direct blebs to the cell front thus underpinning a feedback mechanism that acts in concert with signaling. The examples I give highlight the demand for novel computational and statistical methods for synchronizing single cell dynamics in silico, in time and in space.
