Nejad, S. | bioRxiv Science

bioRxiv2026

Analysis and Design of Frequency-Based Biological Signaling Cascades

Based on our experimental observation of activation state oscillations of different frequencies used to communicate information by the master human stress response regulator protein p38 MAPK 1, we develop a simple graphical approach for understanding and predicting the behavior of complex biological networks acting upon signals carrying information as different frequency waves of chemicals. This approach uses the same techniques used for analyzing and understanding information transmission using waves of electrical currents and fields used in electrical alternating current (AC) circuits. We show how biological components can be organized to behave as standard components found in electronic telecommunications circuits. Finally, we demonstrate how such components can be organized into complex biological signaling cascades whose behavior can be qualitatively and quantitatively understood, and whose output resembles that experimentally observed in p38.

biophysics↗

bioRxiv2025

Human Stress Response Specificity through Bioresonance Selectivity

Bold First ParagraphIn eukaryotes, the mitogen activated protein kinase (MAPK) cascade, a multilayered interconnected network of enzymes, connects external stimuli to gene regulation, determining cellular fate 1. Environmental stress sensed by a cell starts a complex chain of reactions between MAPK enzymes that ultimately activates the master stress response regulator protein p38 MAPK 2,3. Thus activated, p38 must then selectively activate targets from a pool of hundreds to initiate appropriate cellular responses 3. Mechanisms for how p38 performs this selection remain unclear 4,5. Here we show that human p38 target selectivity is based on the same principles as modern electronic telecommunications systems, except using waves of chemicals rather than electromagnetic fields or electric currents. p38 encodes information about stimuli as different frequency oscillations of its activation state, and targets are selected through frequency-dependent resonance of oscillating biochemical reactions between p38 and its targets. We demonstrate this mechanism by activating various genetic responses in human cells by applying only sugar at different frequencies. These results unify observations of oscillating signaling components and altered responses 6-19 into a coherent framework to understand and control human gene expression. As failures of this mechanism may contribute to some p38-associated diseases 2,20-28, these findings may have implications for pharmaceutical development and therapeutic strategies.

biophysics↗