Alan Givré | Searcharxiv

arXiv2024

Qualitatively Distinct Signaling in Cells: The Informational Landscape of Amplitude and Frequency Encoding

Cells continuously sense their surroundings to detect modifications and generate responses. Very often changes in extracellular concentrations initiate signaling cascades that eventually result in changes in gene expression. Increasing stimulus strengths can be encoded in increasing concentration amplitudes or increasing activation frequencies of intermediaries of the pathway. In this paper we show that the different way in which amplitude and frequency encoding map environmental changes endow cells with qualitatively different information transmission capabilities. While amplitude encoding is optimal for a limited range of stimuli strengths, frequency encoding can transmit information with equal reliability over much broader ranges. The qualitative difference between the two strategies stems from the scale invariant discriminating power of the first transducing step in frequency codification. The apparently redundant combination of both strategies in some cell types may then serve the purpose of expanding the span over which stimulus strengths can be reliably discriminated. In this paper we discuss a possible example of this mechanism in yeast.

q-bio.CB↗

arXiv2024

Cell information processing via frequency encoding and excitability

Cells continuously interact with their environment mediating their responses through signaling cascades. Very often, external stimuli induce pulsatile behaviors in intermediaries of the cascade of increasing frequency with the stimulus strength. This is characteristic of intracellular Ca$^{2+}$ signals involving Ca$^{2+}$ release through Inositol Trisphosphate Receptors (IP$_3$Rs). The mean frequency of IP$_3$R-mediated Ca$^{2+}$ pulses has been observed to scale exponentially with the stimulus strength in many cell types. In this paper we use a simple ODE model of the intracellular Ca$^{2+}$ dynamics for parameters for which there is one excitable fixed point. Including fluctuations through an additive noise term, we derive the mean escape rate from the stationary state and, thus, the mean interpulse time, as a function of the fraction, $β$, of readily openable IP$_3$Rs. Using an IP$_3$R kinetic model, experimental observations of spatially resolved Ca$^{2+}$ signals and previous estimates of the IP$_3$ produced upon stimulation we quantify the fluctuations and relate $β$ to [IP$_3$] and the stimulus strength. In this way we determine that the mean interpulse time can be approximated by an exponential function of the latter for ranges such that the covered mean time intervals are similar or larger than those observed experimentally. The study thus provides an easily interpretable explanation, applicable to other pulsatile signaling intermediaries, of the observed exponential dependence between frequency and stimulus, a key feature that makes frequency encoding qualitatively different from other ways commonly used by cells to "read" their environment.

q-bio.CB↗