Combining microcontact printing with particle image velocimetry, live cell imaging and numerical simulations, we have studied the role of cell density, intercel

The closure of gaps within epithelia is crucial to maintain its integrity during biological processes such as wound healing and gastrulation. Depending on the distribution of extracellular matrix, gap closure occurs through assembly of multicellular actin-based contractile cables or protrusive activity of border cells into the gap. Here we show that the supracellular actomyosin contractility of cells near the gap edge exerts sufficient tension on the surrounding tissue to promote closure of non-adherent gaps. Using traction force microscopy, we observe that cell-generated forces on the substrate at the gap edge first point away from the centre of the gap and then increase in the radial direction pointing into the gap as closure proceeds. Combining with numerical simulations, we show that the increase in force relies less on localized purse-string contractility and more on large-scale remodelling of the suspended tissue around the gap. Our results provide a framework for understanding the assembly and the mechanics of cellular contractility at the tissue level.

Yes‐associated protein (YAP) and its paralog WW domain containing transcription regulator 1 (TAZ) are important regulators of multiple cellular functions such as proliferation, differentiation, and survival. On the tissue level, YAP/TAZ are essential for embryonic development, organ size control and regeneration, while their deregulation leads to carcinogenesis or other diseases. As an underlying principle for YAP/TAZ‐mediated regulation of biological functions, a growing body of research reveals that YAP/TAZ play a central role in delivering information of mechanical environments surrounding cells to the nucleus transcriptional machinery. In this review, we discuss mechanical cue‐dependent regulatory mechanisms for YAP/TAZ functions, as well as their clinical significance in cancer progression and treatment.

Mechanical forces play a pivotal role in the regulation of focal adhesions (FAs) where the actin cytoskeleton is anchored to the extracellular matrix through integrin and a variety of linker proteins including talin and vinculin. The localization of vinculin at FAs depends on mechanical forces. While in vitro studies have demonstrated the force-induced increase in vinculin binding to talin, it remains unclear whether such a mechanism exists at FAs in vivo. In this study, using fibroblasts cultured on elastic silicone substrata, we have examined the role of forces in modulating talin-vinculin binding at FAs. Stretching the substrata caused vinculin accumulation at talin-containing FAs, and this accumulation was abrogated by expressing the talin-binding domain of vinculin (domain D1, which inhibits endogenous vinculin from binding to talin). These results indicate that mechanical forces loaded to FAs facilitate vinculin binding to talin at FAs. In cell-protruding regions, the actin network moved backward over talin-containing FAs in domain D1-expressing cells while it was anchored to FAs in control cells, suggesting that the force-dependent vinculin binding to talin is crucial for anchoring the actin cytoskeleton to FAs in living cells.

Tensile forces generated by stress fibers drive signal transduction events at focal adhesions. Here, we report that stress fibers per se act as a platform for tension‐induced activation of biochemical signals. The MAP kinase, ERK is activated on stress fibers in a myosin II‐dependent manner. In myosin II‐inhibited cells, uniaxial stretching of cell adhesion substrates restores ERK activation on stress fibers. By quantifying myosin II‐ or mechanical stretch‐mediated tensile forces in individual stress fibers, we show that ERK activation on stress fibers correlates positively with tensile forces acting on the fibers, indicating stress fibers as a tension sensor in ERK activation. Myosin II‐dependent ERK activation is also observed on actomyosin bundles connecting E‐cadherin clusters, thus suggesting that actomyosin bundles, in general, work as a platform for tension‐dependent ERK activation. Synopsis This study reveals that individual stress fibers work as a platform for activating ERK in a mechanical tension‐dependent manner. Activation of ERK on stress fibers, but not its localization, depends on myosin II activity. External application of tensile force to stress fibers restores ERK activation on stress fibers under inhibition of myosin II. ERK activation on individual stress fibers increases with the magnitude of tensile forces acting on the fibers.