Viscosity-mediated signal amplification enables robust left-right symmetry breaking in the mouse node

Left-right (LR) symmetry breaking in vertebrates depends on a directional fluid flow generated in the embryonic LR organizer, yet how this flow is sensed remains unresolved. Mechanosensing and chemosensing models each capture part of the process but face key limitations when considered independently. Here, we introduce a minimal theoretical model of a downstream viscosity-mediated signal amplification mechanism that unifies these perspectives. In this framework, macromolecules secreted by LR organizer cells generate weak spatial variations in the material composition of the near-surface fluid, thereby locally modifying its rheological properties. Once a sufficiently viscous layer develops, it is entrained by the leftward nodal flow and significantly amplifies the drag and torque exerted on immotile perinodal cilia, enabling robust discrimination of flow direction even when flow magnitudes on the left and right are nearly identical. The model naturally incorporates macromolecule secretion, clarifies the complementary roles of motile and immotile cilia, and addresses several major shortcomings of existing mechanosensing and chemosensing proposals. Rather than explaining the origin of LR asymmetry, our theory provides a physically grounded mechanism by which weak flow-generated asymmetries can be mechanically amplified into a robust developmental signal.