Viscosity-mediated signal amplification enables robust left–right symmetry breaking in the mouse node
File(s)
Published online version
Author(s)
Lee, Chiu Fan
Vermot, julien
Type
Journal Article
Abstract
Left-right (LR) asymmetry is a defining feature of vertebrate development: although the body appears externally symmetric, many internal organs occupy reproducible LR positions. In mammals, LR symmetry breaking is initiated in a transient embryonic structure called the node, where rotating motile cilia generate a leftward fluid flow. Although this flow is known to be essential, how embryos reliably detect it and convert it into a robust developmental decision has remained unresolved. Two main hypotheses have been proposed. One suggests that immotile cilia directly sense the mechanical forces generated by the flow, whereas the other proposes that the flow transports signaling molecules preferentially to the left side of the node. Although both hypotheses are supported by experimental evidence, each faces important challenges when considered in isolation.
Here, we present a minimal theoretical biophysics model showing how these two perspectives can operate together. We propose that macromolecules secreted by cells within the node locally modify the rheological properties of the near-surface fluid. As these molecules accumulate, they create a transient high-viscosity layer that is entrained by the leftward flow, amplifying the hydrodynamic drag and torque experienced by nearby immotile cilia. Consequently, a weak asymmetry in fluid composition is converted into a much stronger mechanical signal, enabling reliable discrimination between left and right even when the flow itself is nearly symmetric. Assuming an initial leftward flow bias has already been established, our model provides a physically grounded downstream amplification mechanism linking flow-driven transport to mechanical sensing. By integrating concepts from fluid mechanics, rheology, and developmental biology, the theory reconciles several experimental observations and suggests new quantitative tests of how physical processes contribute to vertebrate LR symmetry breaking.
Here, we present a minimal theoretical biophysics model showing how these two perspectives can operate together. We propose that macromolecules secreted by cells within the node locally modify the rheological properties of the near-surface fluid. As these molecules accumulate, they create a transient high-viscosity layer that is entrained by the leftward flow, amplifying the hydrodynamic drag and torque experienced by nearby immotile cilia. Consequently, a weak asymmetry in fluid composition is converted into a much stronger mechanical signal, enabling reliable discrimination between left and right even when the flow itself is nearly symmetric. Assuming an initial leftward flow bias has already been established, our model provides a physically grounded downstream amplification mechanism linking flow-driven transport to mechanical sensing. By integrating concepts from fluid mechanics, rheology, and developmental biology, the theory reconciles several experimental observations and suggests new quantitative tests of how physical processes contribute to vertebrate LR symmetry breaking.
Date Issued
2026-09-02
Date Acceptance
2026-08-07
Citation
Newton, 2026
ISSN
2950-6360
Publisher
Cell Press
Journal / Book Title
Newton
Copyright Statement
© 2026 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
License URL
Identifier
10.1016/j.newton.2026.100672
Publication Status
Published online
Article Number
100672
Date Publish Online
2026-09-02