Microtubules may harden or soften cells, depending of the extent of cell distension.

Experimental data show that disruption of microtubules causes cells to either become stiffer or softer. Current understanding of these behaviors is based on several different mechanisms, each of which can account for only stiffening or softening. In this study we offer a model that can explain both these features. The model is based on the cellular tensegrity idea. Key premises of the model are that cell shape stability is secured through pre-existing mechanical stress (prestress) borne by the actin cytoskeletal network, and that this prestress is partly balanced by cytoskeletal microtubules and partly by the extracellular matrix. Thus, disturbance of this balance would affect cell deformability. The model predicts that disruption of microtubules causes an increase or a decrease in cell stiffness, depending on the extent to which microtubules participate in balancing the prestress which, in turn, depends on the extent of cell spreading. In highly spread cells microtubules have a minor and negative contribution to cell stiffness, whereas in less spread cells their contribution is positive and substantial. Since in their natural habitat cells seldom exhibit highly spread forms, the above results suggest that the contribution of microtubules to cell deformability cannot be overlooked.