Simple Rho GTPase Dynamics Generate a Complex Regulatory Landscape Associated with Cell Shape.

Area of Science:

• Cell Biology
• Biophysics
• Computational Biology

Background:

• Migratory cells display diverse shapes influenced by their environment.
• Cytoskeletal regulators Rac1 and RhoA GTPase activity are known to control cell shape.
• Previous studies identified discrete cell shapes and linked them to GTPase activity.

Purpose of the Study:

• To computationally assess if known GTPase dynamics can explain the diversity of cell shapes.
• To investigate how GTPase signaling networks generate spatial signaling states.

Main Methods:

• Utilized computational modeling to simulate GTPase dynamics.
• Analyzed the emergence of distinct signaling phenotypes from model parameters.
• Focused on autoactivation, cross-talk, and membrane binding of GTPases.

Main Results:

• GTPase dynamics, including autoactivation and mutual antagonism, generate diverse homogeneous and polarized phenotypes.
• The model predicts complex multistability with six distinct stable steady states.
• These stable states map to observed cell morphologies, linking signaling to shape.

Conclusions:

• Simple Rho GTPase dynamics can produce a wide array of cell shapes observed in migratory populations.
• Cell shape heterogeneity may reflect underlying signaling dynamics rather than intrinsic cell variation.
• Rho GTPases play a central role in regulating cell shape characteristics and contributing to observed diversity.