Image based modeling of bleb site selection

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.