title: Microtubule depolymerization induces traction force increase through two distinct pathways.
abstract: Traction forces increase after microtubule depolymerization; however, the signaling mechanisms underlying this, in particular the dependence upon myosin II, remain unclear. We investigated the mechanism of traction force increase after nocodazole-induced microtubule depolymerization by applying traction force microscopy to cells cultured on micropatterned polyacrylamide hydrogels to obtain samples of homogeneous shape and size. Control cells and cells treated with a focal adhesion kinase (FAK) inhibitor showed similar increases in traction forces, indicating that the response is independent of FAK. Surprisingly, pharmacological inhibition of myosin II did not prevent the increase of residual traction forces upon nocodazole treatment. This increase was abolished upon pharmacological inhibition of FAK. These results suggest two distinct pathways for the regulation of traction forces. First, microtubule depolymerization activates a myosin-II-dependent mechanism through a FAK-independent pathway. Second, microtubule depolymerization also enhances traction forces through a myosin-II-independent, FAK-regulated pathway. Traction forces are therefore regulated by a complex network of complementary signals and force-generating mechanisms.
authors.affiliation: Department of Biomedical Engineering, Carnegie Mellon University, 700 Technology Drive, Pittsburgh, PA 15219,  USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Rape
authors.forename: Wei-hui
authors.initials: WH
authors.lastname: Guo
authors.forename: Yu-li
authors.initials: YL
authors.lastname: Wang
mesh_terms: D000818:Animals; D048430:Cell Shape / Q000187:drug effects; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D022001:Focal Adhesions; D051379:Mice; D008870:Microtubules / Q000187:drug effects / Q000502:physiology*; D024462:Myosin Type II / Q000037:antagonists & inhibitors; D041681:NIH 3T3 Cells; D015739:Nocodazole / Q000494:pharmacology; D015398:Signal Transduction; D050257:Tubulin Modulators / Q000494:pharmacology
chemical_list: D050257:Tubulin Modulators; D051416:Focal Adhesion Protein-Tyrosine Kinases; D024462:Myosin Type II; D015739:Nocodazole