Work

Frequency-Dependent Premature Differentiation of Pheochromocytoma Cells Exhibits Band-Pass Filter Behavior Correlation with Intracellular Enzyme Activation Kinetics

Year: 2025

Type: article

Abstract: 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.

Source: International Journal of Molecular Sciences

DOI: 10.3390/ijms26115287

Authors: Zubaidah Ningsih, Nguyen H. N. Tran, Andrew H. A. Clayton

Institutions: University of Brawijaya, Swinburne University of Technology, Drexel University

Language: English

Topic: Gene Regulatory Network Analysis

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,499