Membrane binding and unbinding dynamics play a crucial role in the biological activity of several nonintegral membrane proteins, which have to be recruited to the membrane to perform their functions. By localizing to the membrane, these proteins are able to induce downstream signal amplification in their respective signaling pathways. Here, we present a 3D computational approach using reaction-diffusion equations to investigate the relation between membrane localization of focal adhesion kinase (FAK), Ras homolog family member A (RhoA), and signal amplification of the YAP/TAZ signaling pathway. Our results show that the theoretical scenarios in which FAK is membrane bound yield robust and amplified YAP/TAZ nuclear translocation signals. Moreover, we predict that the amount of YAP/TAZ nuclear translocation increases with cell spreading, confirming the experimental findings in the literature. In summary, our in silico predictions show that when the cell membrane interaction area with the underlying substrate increases, for example, through cell spreading, this leads to more encounters between membrane-bound signaling partners and downstream signal amplification. Because membrane activation is a motif common to many signaling pathways, this study has important implications for understanding the design principles of signaling networks.

膜结合和解结合动力学在几种非整合膜蛋白的生物活性中起着至关重要的作用，这些蛋白必须被招募到膜上才能发挥其功能。通过定位到膜上，这些蛋白质能够在它们各自的信号通路中诱导下游信号放大。在这里，我们提出了一种使用反应扩散方程的 3D 计算方法，以研究粘着斑激酶 (FAK)、Ras 同源家族成员 A (RhoA) 的膜定位与 YAP/TAZ 信号通路的信号放大之间的关系。我们的研究结果表明，FAK 是膜结合的理论场景产生稳健和放大的 YAP/TAZ 核转位信号。此外，我们预测 YAP/TAZ 核易位的数量随着细胞扩散而增加，证实了文献中的实验结果。总之，我们的计算机预测表明，当细胞膜与底层底物的相互作用面积增加时，例如，通过细胞扩散，这会导致膜结合信号伙伴和下游信号放大之间的更多相遇。由于膜激活是许多信号通路共有的基序，因此这项研究对于理解信号网络的设计原理具有重要意义。