Scaling mechanical response and proliferation rate with cell size using apical stress fibers

The scaling of the properties of biological systems with their size is central to development and physiology. However, such scaling remains poorly explored in cell mechanics and mechanosensing. By examining how a Drosophila epithelium responds to morphogenetic forces, we identified a class of apical stress fibers (aSFs) anchored to adherens junctions. aSF number scales with cell apical area, in agreement with mathematical models showing that such scaling can prevent larger cells from elongating under mechanical stress. Furthermore, aSFs promote clustering of Hippo pathway components, thereby scaling Hippo activity and thus proliferation rate with area. We found that aSFs nucleate at tricellular junctions (TCJs), then move across the cell before eventually breaking, most often when they encounter another TCJ. This observation motivates a simple geometric mechanism that can quantitatively account for most of the scaling of aSF number with cell size: Because larger cells have more TCJs, they nucleate more aSFs; because these TCJs are typically farther apart, each aSF survives longer before breaking. Development, homeostasis, and repair entail changes in epithelial cell area driven by mechanical forces; our work highlights how, in turn, cell mechanosensitivity scales with cell area.