Ningsih Zubaidah, Tran Nguyen H N, Clayton Andrew H A
Department of Chemistry, Faculty of Mathematics and Natural Sciences, Brawijaya University, Jl. Veteran, Malang 65145, Indonesia.
Department of Physics and Astronomy, Optical Sciences Centre, School of Science, Computing and Emerging Technologies, Swinburne University of Technology, Melbourne, VIC 3122, Australia.
Int J Mol Sci. 2025 May 30;26(11):5287. doi: 10.3390/ijms26115287.
Advances in microfluidics, optogenetics and electronics have enabled the study of dynamically controlled inputs on cellular fate. Here, we applied a microfluidic system to deliver periodic inputs of growth factors to pheochromocytoma cells and measured the extent of premature differentiation as a function of input frequency. Epidermal growth factor-triggered differentiation peaked at two cycles/hour, while nerve growth factor-triggered differentiation peaked at one cycle/hour. To interpret the results, we analyzed a published model that attributed pheochromocytoma cell differentiation to the linear combination of activated enzymes extracellular signal-regulated kinase (ERK), cAMP response element binding protein (CREB), protein kinase B (AKT) and c-Jun N-terminal kinase (JNK) at specific times after step input stimulation. Transfer functions for enzyme activation were derived from the published time-domain activation kinetics and these transfer functions were combined in a parallel architecture as a predictor of neurite outgrowth, as a function of input frequency. Qualitative agreement was observed between the model and the experiments.
微流体技术、光遗传学和电子学的进步使得对细胞命运的动态控制输入进行研究成为可能。在此，我们应用微流体系统向嗜铬细胞瘤细胞输送周期性生长因子输入，并测量过早分化程度作为输入频率的函数。表皮生长因子触发的分化在每小时两个周期时达到峰值，而神经生长因子触发的分化在每小时一个周期时达到峰值。为了解释结果，我们分析了一个已发表的模型，该模型将嗜铬细胞瘤细胞分化归因于在阶跃输入刺激后特定时间激活的酶细胞外信号调节激酶（ERK）、cAMP反应元件结合蛋白（CREB）、蛋白激酶B（AKT）和c-Jun氨基末端激酶（JNK）的线性组合。酶激活的传递函数源自已发表的时域激活动力学，并且这些传递函数在并行架构中组合，作为神经突生长的预测指标，作为输入频率的函数。在模型和实验之间观察到定性一致性。
