Cellular Tango: how extracellular matrix adhesion choreographs Rac-Rho signaling and cell movement

Area of Science:

• Cell Biology
• Biophysics
• Computational Biology

Background:

• Small GTPases Rac and Rho regulate eukaryotic cell shape, influencing protrusion and retraction.
• Cell deformation impacts adhesion to the extracellular matrix (ECM).
• ECM signaling via integrins modulates GTPase activity, creating a feedback loop.

Purpose of the Study:

• To model the three-way feedback loop between small GTPases (Rac/Rho), cell shape, and ECM interactions.
• To investigate emergent cell behaviors in 1D, 2D, and deforming 2D spatial domains.
• To explore the biophysical basis of cell-ECM adhesion and its role in GTPase regulation.

Main Methods:

• Development of a computational model incorporating reaction-diffusion equations.
• Numerical simulations using open-source software (Morpheus).
• Custom-built cellular Potts model simulations with detailed adhesion-bond biophysics.

Main Results:

• Observed diverse spatial patterns and cell behaviors, including persistent polarity, polarity oscillations, and spiral waves.
• Demonstrated that cell shape influences spatial pattern formation.
• Showed that emergent spatial patterns, in turn, affect cell shape.

Conclusions:

• The interplay between Rac/Rho GTPases, cell shape, and ECM signaling generates complex cell dynamics.
• Computational modeling provides insights into the biophysical mechanisms driving cell behavior.
• Cell shape and polarity are dynamically coupled through GTPase-ECM feedback.