Nałecz-Jawecki, P. | Search bioRxiv

bioRxiv2025

Quantifying cancer- and drug-induced changes in Shannon information capacity of RTK signaling

Signaling pathways transmit and process information, enabling cells to respond accurately to external cues. Disease states like cancer can corrupt signal transmission, though the magnitude to which they reduce information capacity has not been quantified. Here we apply pseudo-random pulsatile optogenetic stimulation, live-cell imaging, and information theory to compare the information capacity of receptor tyrosine kinase (RTK) signaling pathways in EML4-ALK-driven lung cancer cells (STE-1) and non-transformed lung epithelial cells (BEAS-2B). The information rate through the RTK/ERK pathway in STE-1 cells was below 0.5 bit/hour but increased to 3 bit/hour after oncogene inhibition. Information was transmitted by only 50-70% of cells, whose channel capacity (maximum information rate) was estimated through in silico protocol optimization. Although oncogene inhibition increased the capacity of the RTK/ERK pathway in STE-1 cells (6 bit/hour), capacity remained lower than in BEAS-2B (11 bit/hour). The capacity of the parallel RTK/calcineurin pathway in BEAS-2B exceeded 15 bit/hour. This study highlights information capacity as a sensitive metric for identifying disease-associated dysfunction and evaluating effects of targeted interventions.

systems biology↗

bioRxiv2024

Information transmission in a cell monolayer: A numerical study

Motivated by the spatiotemporal waves of MAPK/ERK activity, crucial for long-range communication in regenerating tissues, we investigated stochastic homoclinic fronts propagating through channels formed by directly interacting cells. We evaluated the efficiency of long-range communication in these channels by examining the rate of information transmission. Our study identified the stochastic phenomena that reduce this rate: front propagation failure, new front spawning, and variability in the front velocity. We found that a trade-off between the frequencies of propagation failures and new front spawning determines the optimal channel width (which geometrically determines the front length). The optimal frequency of initiating new waves is determined by a trade-off between the input information rate (higher with more frequent initiation) and the fidelity of information transmission (lower with more frequent initiation). Our analysis provides insight into the relative timescales of intra- and intercellular processes necessary for successful wave propagation. Author SummaryIn biological tissues, traveling waves of cellular activity are observed in the process of wound healing when they coordinate cell replication and collective migration. These waves can carry information over long distances. However, random effects on the single-cell level can affect wave propagation and disrupt information flow. In this paper, using a numerical model we classified these stochastic events and quantified the maximum range and frequency of such waves and their capacity to carry information. We discovered that most effective transmission occurs in relatively narrow channels (formed by directly interacting cells), and that the refractory time, in which a cell is resistant to activation by neighboring cells, must be long with respect to the time needed for cell activation. The optimal time intervals between the initiated waves are of order of few refractory times (depending on channel length).

systems biology↗