Pattern formation in the actin cortex and during polarization

One essential feature of cell migration is pseudopod formation, during which the cell memambrane is locally pushed outwards by actin polymerization (1). We study the dynamics and pattern formation in the cortex of Dictyostelium. For eukaryotes it is known that the protein super-family of Ras regulates processes like cell division and polarization (2). We are particularly interested in the physical and biochemical processes and patterns of Ras-G within the cell cortex (3, 4). With a selection of directly or indirectly Ras-interacting fluorescently labeled proteins, we visualize and compare the initial upstream chemotactic signaling with actin polymerization and relate it to pattern selection processes and pseudopod extension. An exemplary crosscorrelation is shown in Figure 1.

Figure 1:

Non-normalized crosscorrelations extracted from kymographs for Ras- G and LimE during chemotactic migration.

Besides signaling pathways of directional sensing and motility, chemotaxis includes polarity, a breaking of the symmetry that gives the cell a leading and retracting edge (5). In a theoretical analysis we study the pattern formation of cell polarity with an emphasis on PTEN and PIP3 singaling, as shown in Figure 2. During spontaneous cell polarization of Dictyostelium cells, phosphatidylinositol (3,4,5)-triphosphate (PIP3) and PTEN (phosphatase tensin homolog) have been identified as key signaling molecules, where randomly triggered excitable PIP3 waves regulate PTEN concentration.

Figure 2:

Simulated traveling waves of PIP3 (green) and PTEN (red) are indistinguishable from the experimental observations by Gerisch et al. (6)

Contact: Fabian Knoch, Christoph Blum, Eberhard Bodenschatz

[1] Driscoll MK, Fourkas JT, & Losert W (2011) Local and global measures of shape dynamics. Phys Biol 8(5)
[2] K. F. Swaney, C.-H. Huang, and P. N. Devreotes, Annu. Rev. Biophys. 39, 265 (2010).
[3] Hecht I, et al. (2011) Activated Membrane Patches Guide Chemotactic Cell Motility. Plos Comput Biol 7(6)
[4] Skoge M, et al. (2010) Gradient sensing in defined chemotactic fields. Integr Biol 2(11-12):659-668
[5] Gerisch G, Ecke M, Wischnewski D, & Schroth-Diez B (2011) Different modes of state transitions determine pattern in the Phosphatidylinositide-Actin system. Bmc Cell Biol 12.
[6] Gerisch G, Schroth-Diez B, Muller-Taubenberger A, & Ecke M (2012) PIP3 Waves and PTEN Dynamics in the Emergence of Cell Polarity. Biophysical Journal 103(6):1170-1178.