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Organized Randomness: How Hierarchical Coupling of an Excitable System and a Bistable Switch Shape Spontaneous Cell
Masahiro Ueda1, Hiroaki Takagi2, Satomi Matsuoka3
1Laboratory of Single Molecule Biology, Graduate School of Frontier Biosciences, The University of Osaka, Suita, Osaka 565-0871, Japan ueda.masahiro.fbs@osaka-u.ac.jp.
Cold Spring Harbor Perspectives in Biology
|April 13, 2026
Summary
Amoeboid cells use Ras GTPase excitability to generate membrane protrusions and cell polarity, enabling exploration. This mechanism converts molecular noise into directed movement for navigating environments.
Area of Science:
- Cell biology
- Biophysics
- Systems biology
Background:
- Eukaryotic cells exhibit autonomous migration and polarity via signal transduction networks.
- Ras GTPase dynamics are crucial for cell excitability and pattern formation.
Purpose of the Study:
- To investigate the role of Ras GTPase and RasGEFX in driving amoeboid cell excitability and polarity.
- To elucidate the molecular mechanisms coupling excitable Ras dynamics to bistable switches for cell behavior.
Main Methods:
- Genetic studies in Dictyostelium.
- Live-cell imaging.
- Analysis of signal transduction networks.
Main Results:
- Ras GTPase and RasGEFX amplify basal Ras activity into propagating waves, initiating pseudopod formation.
- The Ras excitable network engages the PIP3-PTEN switch to stabilize cell polarity.
- A shared mechanism links membrane protrusion and macropinocytosis via the Ras excitable network.
Conclusions:
- A hierarchical excitable-bistable architecture converts intrinsic molecular noise into structured cell behavior.
- This mechanism allows cells to exploit stochasticity for adaptive navigation in complex environments.
- The findings reveal a fundamental strategy for non-Brownian cell movement.
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