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 shapes with detailed adhesion-bond biophysics. 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, spiral waves, and random protrusion-retraction. We show that the observed spatial patterns depend on the cell shape, and vice versa.

已知小 GTPase Rac 和 Rho 可调节真核细胞形状，促进细胞边缘的前突 (Rac) 或后缩 (Rho)。这种细胞变形改变了细胞与细胞外基质 (ECM) 的接触和粘附，而通过整合素受体的 ECM 信号传导也影响 GTPase 活性。我们在 1D 和 2D 空间域中，以及在具有详细粘附键生物物理学的完全变形的 2D 细胞形状中开发并研究了这种三向反馈回路的模型。该模型由使用开源软件 Morpheus 和定制的细胞 Potts 模型模拟数值求解的反应扩散方程组成。我们发现了多种模式和细胞行为，包括持续的极性、翻转的前后细胞极性振荡、螺旋波和随机突出-收缩。