Cofilin is required for polarization of tension in stress fiber networks during migration

Abstract

Cell migration is associated with the establishment of defined leading and trailing edges, which in turn requires polarization of contractile forces. While the actomyosin stress fiber (SF) network plays a critical role in enforcing this polarity, precisely how this asymmetry is established remains unclear. Here, we provide evidence for a model in which the actin-severing protein cofilin participates in symmetry breakage by removing low-tension actomyosin filaments during transverse arc assembly. Cofilin knockdown (KD) produces a non-polarized SF architecture that cannot be rescued with chemokines or asymmetric matrix patterns. Whereas cofilin KD increases whole-cell prestress, it decreases prestress within single SFs, implying an accumulation of low-tension SFs. This notion is supported by timelapse imaging, which reveals weakly contractile and incompletely fused transverse arcs. Confocal and superresolution imaging further associate this failed fusion with the presence of crosslinker-rich, tropomyosin-devoid nodes at the junctions of multiple transverse arc fragments and dorsal SFs. These results support a model in which cofilin facilitates the formation of high-tension transverse arcs, thereby promoting mechanical asymmetry.