title: Generation of contractile actomyosin bundles depends on mechanosensitive actin filament assembly and disassembly.
abstract: Adhesion and morphogenesis of many non-muscle cells are guided by contractile actomyosin bundles called ventral stress fibers. While it is well established that stress fibers are mechanosensitive structures, physical mechanisms by which they assemble, align, and mature have remained elusive. Here we show that arcs, which serve as precursors for ventral stress fibers, undergo lateral fusion during their centripetal flow to form thick actomyosin bundles that apply tension to focal adhesions at their ends. Importantly, this myosin II-derived force inhibits vectorial actin polymerization at focal adhesions through AMPK-mediated phosphorylation of VASP, and thereby halts stress fiber elongation and ensures their proper contractility. Stress fiber maturation additionally requires ADF/cofilin-mediated disassembly of non-contractile stress fibers, whereas contractile fibers are protected from severing. Taken together, these data reveal that myosin-derived tension precisely controls both actin filament assembly and disassembly to ensure generation and proper alignment of contractile stress fibers in migrating cells.
authors.affiliation: Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
authors.forename: Sari
authors.initials: S
authors.lastname: Tojkander
authors.affiliation: Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
authors.forename: Gergana
authors.initials: G
authors.lastname: Gateva
authors.affiliation: Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States.
authors.forename: Amjad
authors.initials: A
authors.lastname: Husain
authors.affiliation: Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States.
authors.forename: Ramaswamy
authors.initials: R
authors.lastname: Krishnan
authors.affiliation: Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
authors.forename: Pekka
authors.initials: P
authors.lastname: Lappalainen
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000205:Actomyosin / Q000378:metabolism*; D045744:Cell Line, Tumor; D006801:Humans; D055595:Mechanical Phenomena
chemical_list: D000205:Actomyosin
keywords: actin; cell biology; human; mechanosensing; stress fibers