Cellular tango: How extracellular matrix adhesion choreographs Rac-Rho signaling and cell movement

TL;DR

This study models the complex feedback between cell adhesion, shape, and Rac-Rho signaling, revealing how these interactions influence cell polarity, movement patterns, and the impact of cell mechanics.

Contribution

It introduces a novel integrated model of cell shape, adhesion, and Rac-Rho signaling, demonstrating their combined effects on cell behavior and pattern formation.

Findings

Patterns depend on cell shape and stiffness.

Cell polarity can be persistent or oscillatory.

Cell mechanics influence migration phenotypes.

Abstract

The small GTPases Rac and Rho are known to regulate eukaryotic cell shape, promoting front protrusion (Rac) or rear retraction (Rho) of the cell edge. Such cell deformation changes the contact and adhesion of cell to the extracellular matrix (ECM), while ECM signaling through integrin receptors also affects GTPase activity. We develop and investigate a model for this three-way feedback loop in 1D and 2D spatial domains, as well as in a fully deforming 2D cell shape. The model consists of reaction-diffusion equations solved numerically with open-source software, Morpheus, and with custom-built cellular Potts model simulations. We find a variety of patterns and cell behaviors, including persistent polarity, flipped front-back cell polarity oscillations, and random protrusion-retraction. We show that the observed spatial patterns depend on the cell shape, and vice versa. The cell stiffness and biophysical properties also affect patterning, overall cell migration phenotypes.