Abstract
Cells often employ fast, pressure-driven blebs to move through tissues or against mechanical resistance, but how bleb sites are selected and directed to the cell front remains an open question. Previously, we found that chemotaxing Dictyostelium cells preferentially bleb from concave regions, where membrane tension facilitates membrane-cortex detachment. Now, through a novel modeling approach based on actual cell contours, we use cell geometry to predict where blebs will form in migrating cells. We find that cell geometry alone, and by implication, physical forces in the membrane, is sufficient to predict the location of blebs in rounded cells moving in a highly resistive environment. The model is less successful with more polarized cells moving against less resistance, but can be greatly improved by positing a front-to-back gradient in membrane-cortex adhesion. In accord with this prediction, we find that Talin, which links membrane and cortex, forms such a front-to-back gradient. Thus our model provides a means of dissecting out the role of physical forces in controlling where blebs form, and shows that in certain circumstances they could be the major determining factor.
Highlights
Dictyostelium cells can use both modes of migration, with blebbing efficiently induced by mechanically resistive environments
Under agar assays were initially developed for mammalian cells[10] and while mimicking some aspects of cell migration in complex 3D environments, such as the increased mechanical resistance, they have the advantage of optical simplicity
Cell contour coordinates were extracted from Dictyostelium cells chemotaxing to cyclic-AMP under 0.7% and 2% agarose
Summary
Dictyostelium cells can use both modes of migration, with blebbing efficiently induced by mechanically resistive environments Such environments can be imposed by forcing cells to chemotax through microchannels[8] or by applying uniaxial pressure to them[9], or as used in this paper, forcing them to move underneath a thin agarose overlay. A variety of mechanisms can be envisioned to direct blebbing to the front of the cell: cortical weakening; global pressure gradients; differences in membrane-cortex linker density; and cell geometry. If local pressure surges were to induce local blebbing, this would be predicted to occur in the rear of the cell, which is not observed, except in the case of Formin-A mutants where the cortex of the uropod is weakened[13]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
