Apical stress fibers enable a scaling between cell mechanical response and area in epithelial tissue – Science Magazine

INTRODUCTION

How biological properties scale with organ or body size is a question fundamental to development and physiology; however, at the cellular level, the scaling between size and properties such as mechanosensitivity remains poorly explored. Mechanosensitivity, the property by which cells sense mechanical forces, plays a fundamental role in proliferation and self-organization. In epithelial tissues, forces sensed at adherens junctions modulate cell behavior via the Hippo/YAP pathway. Although cell geometry, including apical cell area, can vary considerably among cells within a tissue, little attention has been given to whether or how epithelial cells scale their mechanical response to their size or whether such scaling is important for development.

RATIONALE

To probe the interplay between cell size and mechanical response, we first need to better understand how epithelial tissues respond to endogenous forces during morphogenesis. To characterize such tissue response via genetics, imaging, and mechanical perturbations, we used the Drosophila pupal dorsal thorax epithelium as a model system. Because, as in most tissues, cell size varies substantially within this epithelium, it is amenable to the investigation of the possible scaling of mechanosensitivity with cell size.

RESULTS

We observed that in response to morphogenetic forces, cells form apical stress fibers (aSFs), contractile actomyosin bundles that span the cell at the level of the adherens junctions. Through physical modeling and experiments, we found that the number of aSFs per cell scales with cell apical area. This scaling is critical to limit the elongation of larger cells relative to smaller cells under morphogenetic stress, and thus controls the final tissue shape. Moreover, because of the clustering of Hippo components at the tips of aSFs, the scaling of aSF number with cell apical area translates into a scaling between Hippo/YAP activation and cell area; the latter scaling favors the proliferation of larger cells and controls the final number of cells within the tissue.

To identify the “ruler” that enables the scaling of mechanosensitivity with cell area, we explored aSF dynamics. aSFs nucleate at tricellular junctions (TCJs), the position where three cells meet; aSFs then peel from the cortex and often break as they encounter another TCJ. Because both the number of TCJs and the separation between TCJs change as a function of cell area, we hypothesized that TCJs might provide an internal cell “ruler.” Predictions of computer simulations, experimentally tested via the modulation of TCJ number and positions, indicate that the scaling is mainly driven by the number of TCJs and their spatial distribution, which mediate an increase in aSF nucleation rate and lifetime in larger cells.

CONCLUSION

Our work uncovers a scaling between the number of aSFs per cell and cell apical area in response to morphogenetic stress. The number of TCJs and their spatial distribution largely account for this scaling. Thus, our work defines a functional link between TCJs and aSFs. Because TCJs and stress fibers are prevalent biological structures, the molecular characterization of their interplay might shed light on numerous aspects of tissue mechanics, proliferation, and morphogenesis.