J. Colombelli, A. Besser, H. Kress, E.G. Reynaud, P. Girard,
E. Caussinus, U. Haselmann, J.V. Small, U. S. Schwarz, and
E.H.K. Stelzer

Mechanosensing in actin stress fibers revealed by a close correlation
between force and protein localization

Journal of Cell Science April 30 2009

The mechanics of the actin cytoskeleton have a central role in the
regulation of cells and tissues, but the details of how molecular
sensors recognize deformations and forces are elusive. By performing
cytoskeleton laser nanosurgery in cultured epithelial cells and
fibroblasts, we show that the retraction of stress fibers (SFs) is
restricted to the proximity of the cut and that new adhesions form at
the retracting end. This suggests that SFs are attached to the
substrate. A new computational model for SFs confirms this hypothesis
and predicts the distribution and propagation of contractile forces
along the SF. We then analyzed the dynamics of zyxin, a focal adhesion
protein present in SFs. Fluorescent redistribution after laser
nanosurgery and drug treatment shows a high correlation between the
experimentally measured localization of zyxin and the computed
localization of forces along SFs. Correlative electron microscopy
reveals that zyxin is recruited very fast to intermediate substrate
anchor points that are highly tensed upon SF release. A similar acute
localization response is found if SFs are mechanically perturbed with
the cantilever of an atomic force microscope. If actin bundles are cut
by nanosurgery in living Drosophila egg chambers, we also find that
zyxin redistribution dynamics correlate to force propagation and that
zyxin relocates at tensed SF anchor points, demonstrating that these
processes also occur in living organisms. In summary, our quantitative
analysis shows that force and protein localization are closely
correlated in stress fibers, suggesting a very direct force-sensing
mechanism along actin bundles.