Mapfumo Kudzanayi Zebedia, Juma Victor Ogesa, Yigit Gulsemay, Muchatibaya Gift, Madzvamuse Anotida
Mathematics Department, University of British Columbia, 1984 Mathematics Road, Vancouver, British Columbia V6T 1Z2, Canada.
Department of Mathematics, Faculty of Engineering and Natural Sciences, Bahçe¸ Sehir University, Istanbul, Turkey.
R Soc Open Sci. 2025 Apr 3;12(4):241077. doi: 10.1098/rsos.241077. eCollection 2025 Apr.
This study presents a detailed mathematical analysis of the spatio-temporal dynamics of the RhoA-GEF-H1-myosin signalling network, modelled as a coupled system of reaction-diffusion equations. By employing conservation laws and the quasi-steady state approximation, the dynamics is reduced to a tractable nonlinear system. First, we analyse the temporal system of ordinary differential equations (ODE) in the absence of spatial variation, characterizing stability, bifurcations and oscillatory behaviour through phase-plane analysis and bifurcation theory. As parameter values change, the temporal system transitions between stable dynamics; unstable steady states characterized by oscillatory dynamics; and co-existence between locally stable steady states, or co-existence between a locally stable steady state and a locally stable limit cycle. Second, we extend the analysis to the reaction-diffusion system by incorporating diffusion to the temporal ODE model, leading to a comprehensive study of Turing instabilities and spatial pattern formation. In particular, by adding appropriate diffusion to the temporal model: (i) the uniform steady state can be destabilized leading to the well-known Turing diffusion-driven instability (DDI); (ii) one of the uniform stable steady states in the bistable region can be driven unstable, while the other one remains stable, leading to the formation of travelling wave fronts; and (iii) a stable limit cycle can undergo DDI leading to the formation of spatial patterns. More importantly, the interplay between bistability and diffusion shows how travelling wavefronts can emerge, consistent with experimental observations of cellular contractility pulses. Theoretical results are supported by numerical simulations, providing key insights into the parameter spaces that govern pattern transitions and diffusion-driven instabilities.
本研究对RhoA-GEF-H1-肌球蛋白信号网络的时空动力学进行了详细的数学分析,该网络被建模为一个反应扩散方程的耦合系统。通过运用守恒定律和准稳态近似,动力学被简化为一个易于处理的非线性系统。首先,我们分析了在没有空间变化情况下的常微分方程(ODE)时间系统,通过相平面分析和分岔理论来表征稳定性、分岔和振荡行为。随着参数值的变化,时间系统在稳定动力学之间转变;以振荡动力学为特征的不稳定稳态;以及局部稳定稳态之间的共存,或者局部稳定稳态与局部稳定极限环之间的共存。其次,我们通过将扩散纳入时间ODE模型,将分析扩展到反应扩散系统,从而对图灵不稳定性和空间模式形成进行全面研究。特别是,通过向时间模型添加适当的扩散:(i)均匀稳态可能会失稳,导致众所周知的图灵扩散驱动不稳定性(DDI);(ii)双稳区域中的一个均匀稳定稳态可能会被驱动不稳定,而另一个保持稳定,导致行波前沿的形成;(iii)一个稳定的极限环可能会经历DDI,导致空间模式的形成。更重要的是,双稳性和扩散之间的相互作用展示了行波前沿是如何出现的,这与细胞收缩脉冲的实验观察结果一致。理论结果得到了数值模拟的支持,为控制模式转变和扩散驱动不稳定性的参数空间提供了关键见解。