Modelling cell polarization driven by synthetic spatially graded Rac activation

Area of Science:

• Cell biology
• Biophysics
• Computational biology

Background:

• The small GTPase Rac regulates cell polarization, cytoskeletal dynamics, and motility.
• Previous studies linked Rac activation to upstream signaling pathways.
• Understanding Rac's role in cell polarization is crucial for developmental biology and disease research.

Purpose of the Study:

• To develop a minimal reaction-diffusion model for GTPase networks and phosphoinositide crosstalk.
• To investigate the mechanisms underlying Rac-mediated cell polarization.
• To analyze the role of feedback and spatial stimulation in cell polarization.

Main Methods:

• Microfluidic experiments with HeLa cells and rapamycin-induced Rac activation.
• Development of a minimal reaction-diffusion model for GTPase networks.
• Application of Local Perturbation Analysis to model parameter space and behavior.

Main Results:

• Rac activation threshold determines cellular response to gradients.
• Mutual inhibition is a more probable mechanism for cell polarization than positive feedback.
• Spatially uniform stimulation and phosphoinositide-GTPase feedback sensitize cells to gradients.

Conclusions:

• The developed model accurately reflects experimental observations of cell polarization.
• Cellular morphology changes like lengthening/flattening can enhance polarization sensitivity and stability.
• Feedback mechanisms play a significant role in sensitizing cells to external cues.