Shear flow-induced motility ofDictyostelium discoideumcells on solid substrate

Abstract

Application of a mild hydrodynamic shear stress to Dicytostelium discoideum cells, unable to detach cells passively from the substrate, triggers a cellular response consisting of steady membrane peeling at the rear edge of the cell and periodic cell contact extensions at its front edge. Both processes require an active actin cytoskeleton. The cell movement induced by the hydrodynamic forces is very similar to amoeboid cell motion during chemotaxis, as for its kinematic parameters and for the involvement of phosphatidylinositol(3,4,5)-trisphosphate internal gradient to maintain cell polarity. Inhibition of phosphoinositide 3-kinases by LY294002 randomizes the orientation of cell movement with respect to the flow without modifying cell speed. Two independent signaling pathways are, therefore, induced in D. discoideum in response to external forces. The first increases the frequency of pseudopodium extension, whereas the second redirects the actin cytoskeleton polymerization machinery to the edge opposite to the stressed side of the cell. Movies available online

Chemical and mechanical stimuli act on common signal transduction and cytoskeletal networks

“…Similarly to chemotaxing cells, several studies have reported activation and/or localization of typical leading edge markers, including actin polymerization, phosphatidylinositol 3,4,5-trisphosphate (PIP3), and/or extracellular signal-regulated kinase (ERK) 1/2, at the front of cells undergoing either shear-flowmediated migration or electrotaxis (4)(5)(6)(7). However, these activities were observed under steady-state conditions and, because these activities are associated with random projections, their appearance at the leading edge most likely merely reflects the abundance of projections at the front induced by mechanical or electrical forces.…”

Phg2, a Kinase Involved in Adhesion and Focal Site Modeling inDictyostelium

“…We also observed the behavior of phg2 cells in conditions where motility is stimulated by a controlled flow of medium ( Figure 9D) (Decave et al, 2003). This flow is not sufficient to detach the cells, but induces a marked increase in cell motility ( Figure 9E).…”

“…Shear-stress induced motility was determined in a lateral flow chamber according to Decave et al (2003). Briefly, cells were introduced in the flow chamber and adhered during 2 min.…”

Lymphocytes can self-steer passively with wind vane uropods

“…NS, not significant. NATURE COMMUNICATIONS | DOI: 10.1038/ncomms6213 ARTICLE of Dictyostelium discoideum 23 , Entamoeba histolytica 24 and endothelial cells 25 . However, inhibitors of phosphoinositide 3-kinases or G-protein-coupled receptors (Supplementary Note 5 and Supplementary Fig.…”

“…The physiological benefit of flow orientation is currently unknown for lymphocytes and more generally for neutrophils 16 , endothelial cells 9 or amoebae 23 . The fact that neutrophils crawl downstream 16 and T lymphocytes upstream 4 while migrating on the same adhesive ligand, challenges the idea of a universal flowguided mechanism selected to favour extravasation.…”