Figure 10. A working model for mechanosensitive generation of ventral stress fibers in U2OS cells.
(A) Dorsal stress fibers elongate through vectorial actin polymerization from focal adhesions located at the leading edge of the cell, and form a spider net -like structure with multiple transverse arcs. At least Dia1 formin and VASP are involved in vectorial actin polymerization and consequent dorsal stress fiber elongation from focal adhesions. (B) Arcs flow along the elongating dorsal stress fibers towards the cell center, and fuse with each other to form thicker and more contractile actomyosin bundles. (C) Tension provided by the contraction of arcs is mediated through dorsal stress fibers to those focal adhesions that are linked to the end of the arc. This leads to enlargement of ‘terminal’ adhesions and their alignment along the direction of the contractile arc bundle. Tension provided by myosin II –driven contractility of the arc inhibits vectorial actin polymerization in ‘terminal’ focal adhesions, and this is at least partially mediated by VASP phosphorylation. Consequently, elongation of the actomyosin bundle ceases, thus allowing its efficient contractility. Please note that focal adhesions are likely to be composed of many actin filament populations, and for simplicity only the one undergoing vectorial actin polymerization and thus promoting stress fiber elongation is shown in the model. (D) Cofilin-1 specifically binds to and promotes the disassembly of non-contractile dorsal stress fibers, which are connected to the central regions of the arc and thus do not participate in the formation of the ventral stress fiber. (E) Whereas non-contractile stress fibers are disassembled by cofilin-1, contractile stress fibers are protected from tension-sensitive cofilin-1–induced severing. Eventually, this leads to the formation of a contractile ventral stress fiber, which is connected to one large focal adhesion at its each end and aligned perpendicularly to the direction of lamellipodium extension.
Figure 10—figure supplement 1. Differential localizations of Tm1 and Tm5NM1 in focal adhesions at the tips of dorsal and ventral stress fibers.
